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The Federal Agency of Health Protection and Social Development
The Stavropol State Medical Academy
Biology with Ecology Department
Mackarenko E.N.,
Boldyreva G.I.,
Parshintseva N.N.
HEREDITARY DISEASES OF A MAN
Stavropol 2008
ФЕДЕРАЛЬНОЕ АГЕНСТВО ПО ЗДРАВООХРАНЕНИЮ И
СОЦИАЛЬНОМУ РАЗВИТИЮ МИНЕСТЕРСТВА
ЗДРАВООХРАНЕНИЯ РФ
Ставропольская государственная медицинская академия
Кафедра биологии с экологией
The Federal Agency of Health Protection and Social Development
The Stavropol State Medical Academy
Biology with Ecology Department
Э.Н. Макаренко, Г.И. Болдырева, Н.Н. Паршинцева
Mackarenko E.N.,
Boldyreva G.I., Parshintseva N.N.
НАСЛЕДСТВЕННЫЕ ЗАБОЛЕВАНИЯ ЧЕЛОВЕКА
Учебное пособие для студентов англоязычного отделения
HEREDITARY DISEASES OF A MAN
Methodological manual for the students of the English-speaking Medium
Ставрополь 2008
Stavropol 2008
УДК 535.317.68 (07.07)
ББК 54-1,4
М 15
НАСЛЕДСТВЕННЫЕ ЗАБОЛЕВАНИЯ ЧЕЛОВЕКА. Учебное
пособие для студентов англоязычного отделения (на английском языке).
– Ставрополь: Изд-во СтГМА. – 2008. – 51с.
Авторы: Макаренко Элина Николаевна, кандидат медицинских
наук, старший преподаватель кафедры биологии с экологией;
Болдырева Галина Ивановна, старший преподаватель кафедры
биологии с экологией;
Паршинцева Наталья Николаевна, старший преподаватель кафедры
иностранных языков с курсом латинского языка.
Учебное пособие включает в себя основные темы курса «Генетика
человека» для студентов англоязычного отделения. Оно состоит из
следующих
разделов:
«Мутации»,
«Болезни
человека»,
«Хромосомные синдромы» и «Молекулярные болезни».
Рецензенты: Ходжаян Анна Борисовна, доктор медицинских наук,
профессор, зав. кафедрой биологии с экологией СтГМА;
Знаменская Стояна Васильевна, кандидат педагогических наук,
доцент кафедры иностранных языков с курсом латинского языка
СтГМА, декан англоязычного отделения деканата иностранных
студентов.
УДК 535.317.68 (07.07)
ББК 54-1,4
М 15
Рекомендовано к изданию Цикловой методической комиссией
Ставропольской
государственной
медицинской
академии
по
англоязычному обучению иностранных студентов.
© Ставропольская государственная медицинская академия. 2008
УДК 535.317.68 (07.07)
ББК 54-1,4
М 15
HEREDITARY DISEASES OF A MAN. Methodological manual for the
students of the English-speaking Medium (on English). – Stavropol. –
Publisher: Stavropol State Medical Academy. – 2008. – 51 p.
Authors: Mackarenko E.N., Senior Lecturers Biology with Ecology of
Department;
Boldyreva G.I., Senior Lecturers Biology with Ecology of Department;
Parshintseva N.N., Teacher of Latin and Foreign Languages Department of
Stavropol State Medical Academy
Presented methodological manual includes the basic themes of course
“Genetics of a man” for the students of the English-speaking Medium. It
consists of following chapters: “Mutations”, “Human diseases”,
“Chromosomal syndromes”, “Molecular diseases”.
Reviewers: Hodzhayan Anna Boriusoivna, Professor, Doctor of
Medicine, Head Biology with Ecology of Department of Stavropol State
Medical Academy,
Znamenskaya Stoyana Vasilievna, Dean of the English-speaking Medium.
УДК 535.317.68 (07.07)
ББК 54-1,4
М 15
© Stavropol State Medical Academy. 2007
ВВЕДЕНИЕ
Методическое пособие по биологии на английском языке
предназначено для студентов англоязычного отделения. Оно включает
основные темы из курса «Генетика человека».
Цель методического пособия – это знакомство студентов первого
курса с наследственными заболеваниями. Причинами наследственных
заболеваний являются мутации, в начале изложения темы дается
определение
понятия
«мутации»,
приводятся
современные
классификации мутаций, структура генных, геномных мутаций и
хромосомных аберраций. Следующие разделы – это хромосомные
синдромы и молекулярные болезни, наиболее часто встречающиеся в
практической деятельности врача. Эти разделы изложены по плану:
синонимы синдрома, которые можно встретить в литературе;
популяционная частота; минимальные диагностические признаки;
клинические проявления и диагностика наследственного заболевания.
«Генетика человека» вызывает затруднения у первокурсников.
Поэтому в методическом пособии кратко и в доступной форме
изложены теоретические аспекты данной темы. Кроме того, представлен
обширный наглядный материал в виде таблиц, кариограмм, фотографий
больных. В конце методической разработки приводится словарь
медицинской терминологии, которая используется при описании
клинических проявлений наследственных заболеваний.
INTRODUCTION
The methodical manual in biology in English is for students of Englishspeaking medium. It includes the basic themes from a course « Genetics of a
man ».
The purpose of the methodical manual is an acquaintance of the first
year students with hereditary diseases. The reasons of hereditary diseases are
mutations. Concepts of «mutation» are defined at the beginning of a theme
statement. Modern classifications of mutations, the structure of gene, genome
mutations and chromosomal aberrations are given. The following chapters are
chromosomal syndromes and the molecular illnesses most frequently
meeting in practical activities of the doctor. These chapters are stated under
the plan: synonyms of a syndrome, which can be met in the literature;
population frequency; the minimal diagnostic attributes; clinical displays and
diagnostics of hereditary disease.
« The genetics of a man» causes difficulties in the first-year students.
Therefore in the methodical manual it is brief and in the accessible form
theoretical aspects of the given theme are stated. Besides the extensive
evident material as tables, karyograms, and photos of patients is submitted. At
the end of methodical manual the dictionary of medical terminology that is
used at the description of clinical displays of hereditary diseases is resulted.
MUTATIONS
Mutations in a broad sense include all those heritable changes, which
alter phenotype of an individual. Hugo de Vries used the term “mutation” to
describe phenotypic changes, which were heritable. He is, therefore, credited
to have differentiated between heritable and environmental variations.
However, the term mutation is now used in a rather strict sense to cover only
those changes, which alter the chemical structure of the gene at the molecular
level. These are commonly called gene mutations or point mutations. In
practice, sometimes it is rather difficult to distinguish between gene mutations
and structural changes in the chromosomes, because certain structural changes
may have the same phenotypic effects as the gene mutations. Small
deficiencies cannot be discovered by cytological observations. Although on
Drosophila small deficiencies can also be detected in the giant salivary gland
chromosomes, in other organisms the only test for a deficiency is that it will
not revert back to the wild type character. However, gene mutations would be
able to give reverse mutations.
The distinction between point mutations and the chromosomal
aberrations is thus a rather superficial one. If chromosomes are not studied
under the microscope, in certain cases we may not be in a position to say with
certainty whether a particular phenotypic character is due to point mutation or
due to a structural change. Many mutations, described by de Vries in
Oenothera lamarckiana, are now known to be due to certain numerical and
structural changes in the chromosomes. For instance, “giant» mutant in
Oenothera lamarckiana was later found to be due to polyploidy.
Brief History
The earliest record of point mutations dates back to 1791 when Seth
Wright noticed a lamb with unusually short legs in his flock of sheep. Wright
thought that it would be worthwhile having a whole flock of these shortlegged sheep, which could not get over the low stone fence and damage the
crop in the adjacent fields. In the successive generations, this trait was
transferred and a line was developed where all sheep had short legs. This
character resulted from a recessive mutation and the short-legged individuals
were homozygous recessive. Once this mutation occurred in a particular cell,
this will be carried in all the cells descending from this parent cell. This point
mutation was discovered at a time when the science of genetics did not even
have its birth. The short-legged breed of sheep was known as Ancon breed.
The scientific study of mutations started in 1910, when Morgan started
his work on fruit fly, Drosophila melanogaster, and reported white-eyed
male individuals among red-eyed male individuals. Later it was found that
gene responsible for this character is located on sex chromosome (Xchromosome) and expresses itself in a male individual (male individuals have
one X- chromosome and one Y- chromosome; the female has two Xchromosomes). When these rare white-eyed males were crossed to their
sisters, red-eyed females; white-eyed females could also be obtained in some
cases proving that the females involved were heterozygous.
Modern Classifications of Mutations
Mutations are the spontaneous, resistant, indirect, spasmodic changes of a
genotype.
Mutations are:
1) Spontaneous (natural) mutations and induced (artificial) mutations.
Spontaneous mutations happen in the nature without intervention of the
person. The person receives artificial mutations purposefully.
2) Dominant mutations and recessive mutations. Dominant mutation is
phenotypically shown in that organism in which it has arisen. Recessive
mutation will be shown only through some generations. For
phenotypical expression it should be distributed in a population. In the
nature dominant mutations occur less often, than recessive mutations.
3) Somatic mutations and generative mutations. Somatic mutations take
place in cells of a body (somatic cell). These are expressed
phenotypically at that organism at which have arisen and transferred
only at asexual reproduction. Frequently a man uses them in selection
of plants. Generative mutations occur in sexual cells (gametes);
therefore these are expressed phenotypically in the following
generation only. They are handed down only at sexual reproduction.
4) Nuclear mutations and cytoplasmic mutations. Nuclear mutations are
connected to changes of DNA included in chromosomes. Cytoplasmic
mutations are caused by changes extranuclear DNA (1 %). It is located
in mitochondrion, plastid, in the cell center.
5) Morphological, physiological
and biochemical mutations.
Morphological mutations result in change of structure, physiological –
reorganization of functions. Biochemical mutations change a
metabolism. These are connected with infringement of protein
synthesizing, which catalyze the certain type of chemical reactions in
an organism.
6) Useful, neutral and harmful (lethal and semilethal) mutations. Useful
mutations raise viability of an organism. Neutral mutations change the
sign of an organism, but do not influence viability. Lethal mutations are
the harmful mutations sharply lowering viability and resulting in
destruction of an organism. Semilethal mutations are harmful too
lowering viability of an organism and resulting in development of
hereditary diseases.
7) Gene (point) mutations, chromosomal mutations (chromosomal
aberrations), genome mutations. Gene mutations are the changes of a
genotype connected to changes of DNA. They do not result in seen
changes of a hereditary material; therefore refer as point mutations.
Chromosomal aberrations are structural changes of chromosomes.
Genome mutations are numerical changes of chromosomes.
Gene Mutations
Mutations at the molecular level should mean permanent alterations in
the sequences of nucleotides (bases) in the nucleic acids, which form the
genetic material. These alterations in base sequences may be of the following
types: 1) deletion of bases, 2) insertion of bases, 3) inversion of a sequence,
4) replacement of a base pair.
The deletion, insertion and inversion include those changes in base
sequence, which involve breakage and reunion of DNA segments. However,
replacement of a base pair may take place during replication of DNA without
any breakage of DNA. The base pair replacement can be of two types:
transitions and transversions.
Transitions
These are those base pair replacements, where a purine is replaced by
another purine and a pyrimidine is replaced by another pyrimidine. It means
that AT is replaced by GC and vice versa.
Transversions
These are those base replacements, where a purine is replaced by a
pyrimidine and vice versa. It means that CG can be replaced by GC and vice
versa and similarly AT can be replaced by TA and vice versa. Similar changes
can also take place between TA and GC as well as between AT and CG in
booth directions.
A
T
G
C
(a) transitions
A
T
C
G
T
A
G
C
( b) transversions
The base pair changes involved in transitions
and
transversions
are
diagrammatically
represented. The changes involving base
replacements take place due to mistakes in the
incorporation of nucleic acid precursots or due to
mistakes committed during replication. However,
it is realized that among two types of base
replacements, transitions are more frequent than
transversions. For a study of details of molecular
mechanisms involved in each event of transition
or transversion following mutagenic treatments or
during spontaneous mutations, the readers are
advised to consult the author’s advanced book on
Genetics “A Text Book of Genetics”.
The base pair changes lead to changes in protein synthesized on the DNA
template. For example, the disease sickle-cell anaemia is caused due to base
pair replacement leading to replacement of an amino acid of β chain of
haemoglobin.
Structural Changes in Chromosomes
Variations in the structure and number of chromosomes have been
observed in natural populations and could also be produced artificially in a
variety of organisms. These variations have been extensively studied and can
be due to either 1) structural changes or 2) numerical changes.
Structural changes can be of the following types:
1) deficiency, which involves loss of a part of a chromosome,
2) duplication, which involves addition of a part of chromosome,
3) translocation, which involves exchange of segments between nonhomologous chromosomes,
4) inversion, which involves a reverse order of the genes in a part of
chromosome.
These structural changes are diagrammatically represented in table №1,
where two non- homologous chromosomes from the complete set are shown.
Structural abnormalities may be found in both homologous
chromosomes of a pair, or in only one of them. When both homologous
chromosomes are involved, these are called structural homozygotes e.g.
deficiency homozygote, duplication homozygote, etc. If only one
chromosome is involved, this will be called a structural heterozygote. The
constitution of a translocation heterozygote and that of a translocation
homozygote are shown in table №1.
Table № 1
two
non-homologous
chromosomes
deletion
1 2 3 4 5 6
7 8 9 10 11 12
1 2
7 8 9 10 11 12
4 5 6
deletion
duplication
1 2 3 3 4 5 6
7 8 9 10 11 12
addition
translocation
inversion
7 8 3 4 5 6
1
4 3 2 5 6
1 2 9 10 11 12
7 8 9 10 11 12
123456
7 8 9 10 11 12
123456
7 8 9 10 11 12
7 8 3 4 5 6
1 2 9 10 11 12
1 2 3 4 5 6
7 8 9 10 11 12
7 8 3 4 5 6
1 2 9 10 11 12
7 8 3 4 5 6
1 2 9 10 11 12
two pairs of
chromosomes
translocation
heterozygote
translocation
homozygote
Numerical Changes in Chromosomes
Numerical changes in chromosomes or variation in the chromosome
number (genome mutation), can be mainly of two types, namely (1)
aneuploidy and (2) euploidy. Aneuploidy means the presence of chromosome
number, which is different than a multiple of the basic chromosome number.
Euploidy, on the other hand, means that the organism should possess one or
more full sets of chromosomes. Let us imagine that 7 is the basic
chromosome number (x) in a particular class of individuals where the diploid
number (2n) is 14. In this case, the chromosome numbers 2n=15 and 2n=13
would be aneuploids, while those having 2n=7, 21, 28, 35 or 42 would be
euploids. A classification of different kinds of numerical changes in
chromosomes is presented below.
Aneuploidy can be either due to the loss of one or more chromosomes
(hypoploidy) or due to addition of one or more chromosomes to the complete
chromosome complement (hyperploidy). Hypoploidy is mainly due to the loss
of a single chromosome, monosomy (2n-1) or due to the loss of one pair of
chromosomes, nullisomy (2n-2), Similarly, hyperploidy, may involve addition
of either a single chromosome, trisomy (2n+1) or a pair of chromosomes,
tetrasomy (2n+2).
Numerical changes in chromosomes
euploidy
aneuploidy
hypoploidy
monoploidy
diploidy
(x)
(2x)
hyperploidy
polyploidy
(3x, 4x, 5x, 6x etc.)
monosomy nullisomy
(2n-1)
(2n-2)
trisomy
(2n+1)
tetrasomy
(2n+2)
Monosomy: since monosomics lack one complete chromosome, such
aberrations create major imbalance and cannot be tolerated in diploids. These
could be easily produced in polyploids. The polyploids have several
chromosomes of same type and, therefore, this loss can be easily tolerated.
The number of possible monosomics in an organism will be equal to the
haploid chromosome number.
Nullisomy: nullisomics are those individuals, which lack a single pair of
homologous chromosomes, so that the chromosome formula would be 2n-2,
and not 2n-1-1, which would mean a double monosomic. E.R.Sears had
isolated all the 21 nullisomics in wheat.
Trisomy: trisomics are those organisms, which have an extra
chromosome (2n+1). Since the extra chromosomes may belong to any one of
the different chromosomes of a haploid complement, the number of possible
trisomics will be equal to the haploid chromosome number.
Tetrasomy: tetrasomics have a particular chromosome represented in
four doses. Therefore, the general chromosome formula for tetrasomics is
2n+2 rather than 2n+1+1, the later being a double trisomic. All the 21
possible tetrasomics are available in wheat. Besides these tetrasomics, E.R.
Sears was also able to synthesize a complete set of compensating nullisomic
tetrasomics (2n-2+2), where the addition of a pair of homologous
chromosomes would compensate for the loss of another pair of homologous.
Such non- homologous chromosomes, which are able to compensate for each
other, are considered to be genetically related and are called homoeologous
chromosomes.
Euploidy: Euploids can be monoploids, diploids or polyploids. A brief
account of the two types of aberrations in this class namely monoploidy and
polyploidy will be presented below. Since the diploids are normal
individuals, these will not be discussed.
Cytology of haploids: Since in a haploid set, the chromosomes are nonhomologous and have no homologous to pair with, they are found as
univalents at metaphase I of meiosis. Consequently, these univalents
distribute at random during anaphase I. For instance, a haploid in maize
(2n=20) will have 10 chromosomes and the number of chromosomes in a
gamete can range from 0-10. Consequently, considerable sterility will be
found. Moreover, since the univalents are scattered all over the cell, they may
constitute a restitution nucleus including all the chromosomes and may thus
give rise to gametes having a complete haploid set of chromosomes. Haploids
(polyhaploids; n=3x=21) were used by E.R. Sears for the production of
monosomics by pollinating the haploid by pollen from a diploid individual
(hexaploid; 2n=6x=42). If the egg has a chromosome number less that the
complete set, this will result into an aneuploid.
Polyploidy: There are mainly three different kinds of polyploids, namely
1) autopolyploids, 2) allopolyploids. Let us imagine that A, B1, B2, and C are
four different haploid sets of chromosomes and that genomes B1 and B2 are
related. Different kinds of polyploids using these genomes are derived.
Autopolyploids: Autopolyploids are those polyploids, which have the
same basic set of chromosomes multiplied. For instance, if a diploid species
has two similar sets of chromosomes or genomes (AA), an autotriploid will
have three similar genomes (AAA), and an autotetraploid will have four such
genomes (AAAA).
Allopolyploids: Polyploidy may also result from the doubling of
chromosome number in a F1 hybrid which is derived from two distinctly
different species. This will bring two different sets of chromosomes in F 1
hybrid. The number of chromosomes in each of these two sets may differ. Let
A represent a set of chromosomes (genome) in species X, and let B represent
another genome in a species Y. The F1 will then have one A genome and
another B genome. The doubling of chromosomes in this F1 hybrid (AB) will
give rise to a tetraploid with two A and two B genomes. Such a polyploid is
called an allopolyploid or amphidiploid.
HEREDITARY DISEASES
On the basis of the importance of hereditary and environmental factors
all human diseases are divided on 3 groups:
●
●
●
hereditary pathology;
diseases with hereditary predisposition (DHP);
nonhereditary illnesses.
The reason of hereditary diseases is mutations. Environmental factors
can change the expression of clinical symptoms and character of the illness
current, therefore they influence only on gene’s expressivity*.
hereditary diseases
=
genome
environmental factors
on expressivity
Molecular diseases and chromosomal syndromes are hereditary
pathology. 50 % from them are congenital diseases. Their other half can be
expressed on different stages of postembryonic period of ontogenesis
according to terms of gene’s expressivity:
● in childhood – mucoviscidosis, Duchenne's pseudohypertrophic
muscular dystrophy, etc.;
● in mature – myotonic dystrophy, Huntington's hereditary chorea;
● in old age – Alzheimer's disease.
Hereditary diseases (more than 2.000)
molecular
illnesses
chromosomal
syndromes ≈ 750
Illnesses with hereditary predisposition (DHP): their development is
determined equally both genome and environmental factors.
DHP
= genome + environmental factors
penetrance
Such illnesses are phenotypically expressed after contact of a mutant
gene with the certain environmental factors promoting penetrance* of
abnormal genes. Therefore, they are called multifactor diseases
(atherosclerosis, essential hypertension, tuberculosis, eczema, psoriasis, etc.)
Multifactor diseases
Monogenic
character
Polygenic
character
Multifactor diseases can be expressed both at children and at adults.
The reason for nonhereditary illnesses is environmental factors. Burns,
traumas, the infectious diseases, harmful habits form this group of diseases.
Genetic factors can influence only on the current of pathological process (on
recovery, regenerative processes, compensation of dysfunctions).
nonhereditary
illnesses
=
environmental factors
genome
influence on
current of
pathological
process
Sometimes nonhereditary illnesses can be shown at a birth. Then they are
similar to hereditary diseases in phenotypical expression (phenocopy*). So,
the congenital malformations arisen in result of teratogenesis effect of
external factors (physical, chemical, biological genesis) during antenatal
period. Congenital malformations caused by agents of syphilis, rubella have a
lot of similarity with chromosomal syndromes.
There is a genetic classification of hereditary illnesses (N.P. Bochkov,
2001). It includes 5 classes:
Hereditary diseases:
1 Gene illnesses;
2 Chromosomal illnesses;
3 Illnesses with hereditary predisposition;
* 4 Genetic illnesses of somatic cells;
* 5 Illnesses with genetic incompatibility of mother and
fetus
* Genetic illnesses of somatic cells are allocated into separate groups
recently. Occasion has served the detection in cells of the specific
chromosomal reorganizations causing oncogenes activation of malignant
tumors, for examples retinoblastoma, Wilms tumor. There are some evidences
that sporadic cases of congenital anomalies are results of mutations in somatic
cells during the critical ontogenesis periods. It is rather probable, that
autoimmune processes and old age can be attributed from same category of a
genetic pathology.
* Illnesses with tissues incompatibility of mother and a fetus are a
result of immune reactions of mother’s organism on fetus antigens. The most
typical and well investigated disease from this group is congenital haemolytic
icterus, for instance, Rhesus-factor incompatibility in pregnant female
(Rhesus blood group – negative) and a fetus (Rhesus blood group – positive).
Also immune conflicts arise at incompatible combinations of antigens and
antibodies on ABO blood groups in mother and a fetus.
Chromosomal illnesses
The reasons: structural and numerical changes of chromosomes
(chromosomal aberrations or genome mutations).
Frequency of occurrence: 0, 7 % in human populations among
newborns.
60 % are genome mutations: Aneuploidy among them is prevailing,
because polyploidy or monoploidy in a man are incompatible with a life. It is
counted up, that 10 % embryos at medical abortions and 25 % at spontaneous
abortions – polyploid organisms. As a rule, aneuploidy has sporadic character.
40 % are chromosomal aberrations.
Chromosomal aberrations
intrachromosomal
interchromosomal (translocations)
balanced
(transpositions, inversions)
unbalanced
(deletions, duplications)
all gene’s loci are present in
genome, but in the other order
some gene’s loci are lost or
doubled
phenotypic deviations are
insignificant
the pathological phenotype is
formed
50 % of structural reorganizations have family character.
Clinical displays:
1) plural congenital anomalies of development;
2) retardation of growth and physical development;
3) backlog in mental development;
4) disorders of nervous system and endocrine glands;
5) high lethality (6 % among index of perinatal mortality, 95-98 % among the reasons of spontaneous abortions).
The mechanism of development. Mutations can arise:
● in gametes of parents → disorders of chromosomal set in all cells →
abnormal organisms → bright clinic expression
● in somatic cells on early stages of embryogenesis → abnormal
chromosomal set in a part of cells (as well autosomes as sexual chromosomes)
→ mosaic organism (somatic mosaicism) → the erased clinic expression.
Sometimes the abnormal cells number in organism is very little. Such
individuals are normal in phenotypical expression.
Feature: autosome disorders proceed more hardly, than anomalies of
sexual chromosomes. Chromosomal anomalies meet on 25 % more in
premature newborns, than in full-term newborns.
Diagnostics: 1) research of a phenotype;
2) clinical observations;
3) genealogic method (it is especially used at chromosomal
aberrations);
4) cytogenetical analysis (definition of sex chromatin, karyotype)
– it is predominantly performed at genome mutations;
5) dermatogliphic research;
6) pathoanatomical descriptions.
CHROMOSOMAL SYNDROMES
1. The chromosomal diseases caused by chromosomal aberrations:
1.1. "Cat-like cry syndrome”
1.2. Translocation form of Down’s syndrome
1.3. Syndrome of “Philadelphian chromosome”
1.4. Martin – Bell's syndrome
2. The chromosomal diseases caused by genome mutations in
autosomes:
2.1. Patau syndrome
2.2. Edwards's syndrome
2.3. Down’s syndrome
3. The chromosomal diseases caused by genome mutations
allosomes:
in
3.1. Turner’s syndrome
3.2 Klinefelter’s syndrome
3.3 X– trisomy syndrome ( X – polysomy)
3.4 Y – trisomy syndrome ( Y – polysomy)
1.1
"Cat-like cry syndrome”
Synonym: Chromosome 5p-syndrome.
J. Lejeune described it in 1963.
Reason: deletion of a short arm of the 5-th chromosome.
Population frequency – 1 : 50 000 newborns.
Minimal diagnostic attributes: unusual cry reminding cat's meowing;
microcephaly*; antimongoloid set of the eyes*; mental retardation; deletion
of a short arm of the 5-th chromosome (Fig. 1.).
Clinical characteristic. The most typical attributes are specific crying (98
%), low birth weight (72 %), growth retardation (85 %), microcephaly* (98
%), intellectual backwardness (100 %), muscular hypotonia* (60-80 %),
moon-like face (70 %), facial asymmetry (25 %), wide nose bridge (84 %),
micrognathia* (75-85 %), malformed low-set auricles (85 %), abnormal
occlusion (70-80 %), high palate (50-75 %), anomalies of larynx (55-65 %),
hypertelorism* (90-95 %) or hypotelorism, epicanthus* (85-90 %),
Fig. 1.
• Moon-like face;
• Epicanthus*;
• Antimongoloid set of the
eyes*;
• Microcephaly*
antimongoloid set* of the eyes (75-85 %) or mongoloid set* of the eyes,
strabismus*, usually divergent strabismus (60-70 %), congenital heart
diseases (15-30 %), short metacarpal and metatarsal bones (65-75 % in an
adult), transversal palmar fold (80-90 %), distal axial triradius (80-90 %), flatfoot (65-75 %), clinodactyly*, partial syndactyly* (25-30 %), decreased
wings of iliac bones or increased iliac angle (70-80 %), scoliosis* (55-65 %),
inguinal [groin] hernia (25-30 %), divergence of direct abdominal muscles
(30-35 %), short neck (45-55 %). Sometimes cryptorchism* and anomaly of
kidneys are met. The patients are inclined to infectious diseases of upper
respiratory tracts. It is necessary to note, that in most cases such attributes as
the cat's meowing, a muscular hypotonia*, moon-like face completely
disappear with age. Frequently simple deletion of a short arm of the 5-th
chromosome is present. The typical phenotype, apparently, is caused by
deletion of a site р14 – р15. Sometimes mosaicism or the 5-th ringchromosome is found. Approximately in 10-15 % of cases the syndrome is
connected with translocation.
Diagnostics: karyotype research and detection of morphologically
changed 5-th chromosome.
1.2
Translocation form of Down’s syndrome
Reason: translocation of the additional 21-st chromosome on the 15- th
or either the 21-st. Karyotype of these patients contains 46 chromosomes.
Therefore, two chromosomes from the 21-st pair are normal, one the 15-th is
normal too, but another – “abnormal large chromosome”. It represents
connection with the additional 21-st chromosome. Other translocation form
can be connection among themselves two 21-st chromosomes from three,
taking place in a chromosomal set.
Clinical characteristic. As a rule, the clinical symptoms of genome
variant and translocation form are practically indiscernible.
If translocation form of Down’s syndrome takes place, one of parents of
the sick child has balanced translocation one of chromosomes of the 21-st pair
on the 15-th or another 21-st chromosome. During gametogenesis the part of
gametes of such parent can receive both the normal 21-st chromosome and
translocational chromosome. In a result, at fertilization of an abnormal gamete
by normal, the zygote containing three 21 chromosomes develops.
If Down’s syndrome (trisomy variant) is met, as a rule, in elderly
mothers, translocation forms of Down’s syndrome are equally characteristic
both for young and for mature age. The risk of birth of a sick child in parents,
one of which carries balanced translocation of the 21-st chromosomes, is
much above than at trisomy form.
Diagnostics: is similar to trisomy variant. At the following pregnancy
amniocentesis is obligatory, if young parents have the child with Down’s
syndrome.
1.3
Syndrome of “Philadelphian chromosome”
For the first time Tooge described it in Philadelphia city (USA) in 1961.
Fig.2.
Blood smear and abnormal
karyotype at chronic
myeloleukemia
Reason: the 21-st chromosome loses the half of a long arm. So was
considered till 1970. For last 30 years character of an aberration was
specified. So translocations of deletion fragment of a long arm of the 22
chromosomes on a long arm of the 9-th chromosome, and a small fragment of
the 9-th on the 22-nd – t (9; 22) (q 34; q 11) take place. Thus the structures
possessing oncogenesis properties are formed (Fig.2.).
Clinical characteristic. Chronic myeloleukemia* is developed. It is
expressed in impetuous duplication of granulocytes (one of leukocytes kinds).
As a result, many immature forms of these leukocytes appear in peripheral
blood.
Diagnostics: detection of a corresponding aberration at karyotype
research.
1.4
Martin -Bell's syndrome
Synonym: X- chromosome fragile syndrome.
C. Lubs described the syndrome in 1968.
Reason: deletion of a short arm of the Х-chromosome in a segment q28.
Population frequency – 0, 5 : 1 000.
Type of inheritance – X – linked recessive.
Minimal diagnostic attributes: moderate or deep mental retardation;
burdock-like ears, jutting out forehead and a massive chin; macroorchism*
(Fig. 3.).
Clinical characteristic. At a birth the weight and length of a body are
normal or exceed norm, the circumference of a head is increased. Ears are
burdock-like. In adolescents the face is rectangular with a high jutting out
forehead, thin long nose, hyperplasia* of mandible. Wide hands are
characteristic. There are a high palate and submucous cleft of the palate or
uvula. The middle otitis* is marked quite often. Intellectual and speech
retardation is typical. Sometimes spasms, changes on cardiogram, muscular
hypotonia*, autism* and hyperactivity are observed. Macroorchism* is
expressed with age of puberty. There are adiposity, gynaecomastia*,
hypospadias* and soft extensible skin. The weakness of the ligament
apparatus of a knee and ankle-joints, prolapse of the mitral valve take place.
Fragility of the Х-q28 is found out at cytogenetical research. Intelligence is
probably decreased in females-carriers. In male-hemizygote – clinical
symptoms can be absent. Correlations between expression of clinical
spectrum and presence of cytogenetical markers are not revealed.
Fig. 3.
Rectangular face; thin long nose and hyperplasia* of mandible;
macroorchism*
Diagnostics: karyotype research and detection of morphologically
changed X-chromosome.
2.1
Syndrome Patau
Synonym: Chromosome 13 trisomy syndrome.
K. Patau described the syndrome in 1960.
Reason: trisomy of the 13-th chromosomes.
Population frequency - 1 : 7 800.
Minimal diagnostic attributes: microcephaly*; polydactyly*; cleft of the
lip and palate (Fig.4.).
Clinical characteristic. Microcephaly* (58,7 %), trigonocephaly*,
narrow palpebral fissure, wide nose basis, sunken bridge of the nose, low
placed and deformed auricles (80 %), micrognathia* (32,8 %), cleft of the lip
and palate (68 %), epicanthus*, microphthalmia* (77 %), coloboma* (35,5
%), short neck, polydactyly* (50 %), flexor position of fingers (44,4 %), long
convex nails, transversal palmar fold are marked at trisomy-13. The internal
defects include:
Fig.4.
Microcephaly*;
polydactyly*;
cleft of the lip and palate.
arrhinencephaly* (63,4 %), aplasia* of a calloused body (19,3 %), cerebellum
hypoplasia* (18,6 %); congenital heart anomalies (80 %) – the defect of
ventricular septum (49,3 %) or the defect of atrial septum (37,6 %);
anomalies of kidneys (58,6 %) – cysts
or double renal pelves, hydronephrosis*
or ureter duplication; the defects of
digestive tract development (50,6 %) –
incomplete intestinal rotation, Mekkel’s
diverticulum. There are cryptorchism*,
hypoplasia* of external genitals,
hypospadias*, two-horned uterus or
reduplication of uterus and vagina.
Syndrome Patau is met in several
cytogenetical variants: simple trisomy
of the 13-th chromosome, Robertson’s
translocation D/13 and mosaicism. The
last variant is less common.
Diagnostics: ♦ karyotype research and detection of trisomy of the13-th
chromosome;
♦ typical dermatogliphic signs: – transversal palmar fold;
– atd -angle is approximately 108°.
2.2
Edwards's syndrome
Synonym: Chromosome 18 trisomy syndrome.
J. Edwards described the syndrome in 1960.
Reason: trisomy of the 18-th chromosome.
Population frequency – 0, 14 : 1 000.
Sex ratio – М 1: F 3.
Minimal diagnostic attributes: multiple defects of development;
retardation of psychomotor development (Fig.5.).
Fig.5.
Malformed low-set ears; prominent back of the head; elongated
back
of micrognathia*;
the head
skull;
short palpebral fissure; microstomia*;
clenched fingers; the fifth finger overlapping on the fourth finger.
Clinical characteristic. Weak activity of a fetus, a small placenta (50 %),
the single umbilical artery (80 %), hydramnion* are typical. An average
weight of the newborn is 2.340 gramme.
There are retardation of psychomotor development (100 %), a skeletal
musculature hypoplasia* and hypoplasia* of a hypodermic adipose tissue (50
%), cryptorchism* (100 %), congenital heart diseases (90 %) – defect in the
ventricular septum and open arterial Botallo’s duct, malformed low-set ears
(80 %), prominent back of the head, elongated skull (80 %), high palate (80
%), micrognathia* (80 %), short palpebral fissure (50%), microstomia*
(50%), flexor fingers deformations (80 %), clenched fingers (50 %), the fifth
finger overlapping on the fourth , the second finger – on the third (50 %); nail
hypoplasia* especially on V-finger and V-toe (50 %), short I-toe (50-80 %),
short sternum (80 %), papilla hypoplasia* and papilla hypertelorism* (50 %),
small pelvis (80 %), restriction of a thigh abduction (80 %), hypotonia*
changing by hypertension (50-80 %), short neck (50-80 %), inguinal or
umbilical hernia, prolapse of the rectum (50-80 %), distal triradius (50-80 %),
abnormal development of kidneys [more often horseshoe-shaped kidney,
hydronephrosis* and hydroureter (50-80 %)], very straightened I -finger (4060 %), additional skin fold on neck (40-60 %), foot with calcaneum-valgus
deformation (40-60 %), Mekkel’s diverticulum (40-60 %), high localization
of a diaphragm (10-50 %), ptosis* (10-50 %), short labrum (10-50 %),
pathology of cerebrum or spinal cord (10-50 %), pylorostenosis* (10-50 %),
partial syndactyly* (10-50 %), ulnar or radial deviation of a hand (10-50 %),
the single palmar fold (10-50 %), the single flexor fold on V-finger (10-50
%), incomplete intestinal rotation (10-20 %), meningomyelitis (10-20 %),
cleft of the lip or palate (10-20 %), choana atresia (10 %), tracheoesophageal
fistula (10 %).
Sometimes macroclitoris, two-horned uterus, ovary hypoplasia*, anus
atresia*, funnel-shaped anus, hip dislocation, phocomelia*, stenosis* of
external acoustic duct with hearing loss, claw-shaped deformation of hand,
haemangioma*, hypoplasia* of thymus, adrenal and thyroid glands,
hemivertebrae, scoliosis*, rib anomaly, union of the vertebrae are marked.
Diagnostics: karyotype research and detection of the 18-th chromosome
trisomy.
2.3
Down’s syndrome
Synonym: Chromosome 21 trisomy syndrome.
J. Down described the syndrome in 1866.
Reason: trisomy of the 21- st chromosomes.
Population frequency – 1 : 700.
Sex ratio – М 1: F 1.
Minimal diagnostic attributes: mental retardation, muscular hypotonia*,
flat face, mongoloid set* of the eyes (Fig.6.).
Clinical characteristic. There are flat face (90 %), mongoloid set* of the
eyes (80 %), epicanthus* (80 %), open mouth (65 %), short nose (40 %), flat
nose bridge (52 %), strabismus* (29 %), pigmentary spots on the edge of the
iris – Brushfeeld’s stains (19 %), brachycephaly* (81 %), flat back of the
head (78 %), displastic ears (43 %), arcual palmar (58 %), teeth anomalies (65
%), striated tongue (50 %), cataract in the age of more than 8 years (66 %),
short broad neck (45 %), dermal fold on the neck in newborns (81 %), short
limbs (70 %), V-finger clinodactyly* (66 %), high mobility of joints (80 %),
congenital heart diseases (40 %), transversal palmar fold (45 %). All patients
are mentally retarded. Atresia* or stenosis* of a duodenum and leukemia are
observed in 8 % of cases.
Fig.6.
Phenotype of siсk children with
Down’s syndrome
The length of human life is determined by presence of defects of the
gastrointestinal tract and heart. The most common form of Down’s syndrome
is the simple trisomy form of the syndrome (94 %). The translocational form
is marked in 4 % of cases, the mosaic form – in 2 %.
Diagnostics: ♦ karyotype research and detection of the 21-st
chromosome trisomy;
♦ typical dermatogliphic signs: – transversal palmar fold;
– atd -angle is more 80°.
3.1.
Syndrome Shereshevskiy – Turner
Synonym: Chromosome X monosomy syndrome; ХО – syndrome;
Turner’s syndrome
Reason: full or partial monosomy of the Х-chromosome.
Population frequency – 2 : 10 000.
Minimal diagnostic attributes: edema of hands and feet in newborns;
hypotonia* of newborns; dermal folds on the neck; short height; congenital
heart diseases; primary amenorrhea* (Fig.7.).
Fig.7.
Edema of hands and feet in newborns;
dermal folds on the neck; broad chest
Clinical characteristic. Typical attributes of Turner’s syndrome are low
growth (98 %), wing-like dermal folds on the neck (56 %), broad chest (60
%), X-shaped curvature of genua (56 %), sexual infantilism (94 %), primary
amenorrhea* (96 %), sterility (99 %). An average adult’s height is 140cm. In
40 % of cases peripheral lymphatic edema of hands and feet in newborns are
observed. Short neck (71 %), epicanthus* (30 %), the low line of a hair
growth on the back of the head (73 %), hypoplasia* or hypertrophy* of nail
plates (73 %), short metacarpal bones (especially IV) or metatarsal bones (44
%), high pigmentation of skin (60 %), high palate (39 %), decreased acuity of
vision (22 %), hearing impairment (52 %), micrognathia* (40 %), funnelshaped chest (38 %), anomaly of urinary system (38 %) are marked. From
defects of cardiovascular system (15 %) coarctation* of aorta and ventricular
septum defect, arterial hypertension (27 %) are most frequently met. In 16 %
of cases intellectual development is reduced. Less frequent and less important
diagnostic signs are – ptosis*, nipples hypoplasia*, hypertelorism*, anomaly
of ribs and long tubular bones, osteoporosis*. The changes of
dermatoglyphics include the distal displacement of triradius, transversal
palmar fold and other features. The risk of thyroiditis, probably, autoimmune
genesis and diabetes is high.
Diagnostics: ♦ karyotype research and detection of full or partial
monosomy of the Х-chromosome, therefore, karyotype- 45, ХО;
♦ research of Barr body; at Shereshevskiy – Turner syndrome Barr
bodies are not found out.
3.2
Klinefelter’s syndrome
Synonym: Chromosome XXY syndrome
H. Klinefelter described it in 1942.
Reason: trisomy or tetrasomy on the Х-chromosome in a male organism.
Population frequency - 1: 1 000 boys.
Minimal diagnostic attributes: hypogonadism*, hypogenitalism*,
karyotype 47, XXY (Fig.8.).
Fig.8. Phenotype and karyotype at Klinefelter’s syndrome
Clinical characteristic. The patients are tall with disproportionate long
limbs. In the childhood they differ by a fragile constitution. Adiposity
develops in the adults. Distinctive attributes of the syndrome are testicles and
penis hypoplasia*. The secondary sexual attributes are poorly developed.
Mature female pattern of hair distribution and gynaecomastia* (50 %) can be
observed. At histological research of testicles hyalinosis*, fibrosis of
seminiferous tubules and secondary hyperplasia* of Leidig’s cells are found
out. Reduction of a sexual inclination, impotence and sterility are typical. The
small deformations of helix, low line of a hair growth on the back of the head,
brachycephaly*, V-finger clinodactyly*, transversal palmar fold, ulna-radial
synostosis, scoliosis, neurological symptoms – spasms, ataxy*, tremor are
possible. At 15-20 % of patients the coefficient of intelligence is lower than
80.
Diagnostics: ♦ karyotype research and detection of superfluous
number of the X-chromosomes in male organism, therefore, karyotype may
be 47, ХХУ or 48, ХХХУ;
♦ research of Barr body; in male organism Barr bodies are found out at
Klinefelter’s syndrome;
♦ typical dermatogliphic signs: – transversal palmar fold;
– atd -angle is 40 – 42 °.
3.3
Syndrome of trisomy (polysomy) on the X-chromosome
For the first time the syndrome was described by Jecobs in 1959
(England).
Reason: superfluous number of the X-chromosomes in female karyotype.
Trisomy (47, XXX) takes place more often, tetrasomy (48, XXXX) takes
place less often and pentasomy (49, XXXXX) is absolutely rare.
Population frequency – 1 or 1,4 on 1 000 born girls.
Clinical characteristic. At trisomy (47, XXX) female phenotype can be
normal. However, the definite degree of intellectual retardation is marked.
Besides, presence of the additional X-chromosomes increases risk of
development of psychical diseases (especially schizophrenia or psychoses) in
2 times. At a part of patients typical hysterical features of a behavior take
place. Occasionally ovary dysfunction, amenorrhea (absence of menses) and
sterility are observed at trisomy. Similar attributes and a various degree of
mental retardation – from moderate backwardness up to heavy moronity – are
more often met at tetra- and pentasomy for the Х-chromosome.
Diagnostics: ♦ karyotype research and detection of superfluous number
of the X-chromosomes in the female organism;
♦ search of the sex X-chromatin (presence of additional Barr bodies in
somatic cells).
3.4
Syndrome of the additional Y-chromosomes
Reason: the additional У-chromosome in male karyotype.
Population frequency – 1 : 1000 newborn boys.
Clinical characteristic. High growth of males is characteristic (average
growth approximately 186 cm). Sometimes acromegaly* traits as a large nose,
the big lips, increased bottom of jaw, etc. are marked. The intelligence may be
normal or insignificantly reduced. Individuals with corresponding karyotype
are inclined to asocial acts, because these males are very aggressive.
Therefore, they are frequently found in prison. Them reproductive function
basically does not suffer. However, there is increased infancy death rate
among children, in which fathers are with additional Y-chromosome. Their
offsprings usually have the normal karyotype, but sometimes sons are born
with karyotype XYY.
Diagnostics: ♦ detection of the Y-chromatin by a fluorescent method;
♦ at karyotype research – one (47, XYY) or more number of the additional Y
– chromosomes (48, XYYY) are determined.
MOLECULAR (gene) DISEASES
Suppose a mutation destroys a crucial part of the genetic code for a
protein essential to life. An organism that fails to produce an active form of
that protein will die prematurely, and the responsible allele is called a lethal
allele.
Dominant lethal alleles are possible, but most are rapidly eliminated.
Exceptions are those not usually expressed until after the individual has
passed reproductive age, in which case the allele is passed on to half of the
offspring, on average. (An example is Huntington’s disease in humans, not
usually expressed until age 35 or later.)
Recessive lethal alleles, on the other hand, are eliminated by selection
only when they occur in homozygotes. These alleles usually occur
heterozygously, masked by a dominant allele that permits the individual to
survive and pass on the recessive lethal allele to future generations. A lethal
allele may even become quite common if it is closely linked to an
advantageous allele of another gene or if the heterozygous condition has some
advantage, as in the case of sickle haemoglobin, discussed shortly. It has been
calculated that the average human is heterozygous for perhaps three to five
lethal recessive alleles. This is part of the reason that marriages between close
relatives produce a disproportionate frequency of offspring with lethal
inherited traits.
Sometimes just one copy of a normal allele does not make enough of its
protein to produce the normal phenotype. In this case the normal allele shows
incomplete dominance to the lethal allele, and the heterozygote has a different
phenotype from either homozygote. An example in humans there is the lethal
allele that causes the middle bone in the fingers of heterozygotes to be
unusually short, a condition called brachydactyly (brachy = short; dactyl =
finger or toe). This makes the fingers appear to have only two bones instead
of three. In homozygotes, this allele results in abnormal development of the
skeleton. Homozygous babies lack fingers and have other skeletal defects that
cause death in infancy.
In a marriage between two brachydactylic people, each child has a onefourth chance of being homozygous for the lethal allele and dying as an
infant; a one-half chance of being a brachydactylic heterozygote; and a onefourth chance of not inheriting an allele for brachydactyly. This 1:2:1
offspring ration is typical of a monohybrid cross involving incomplete
dominance.
Some lethal alleles are mutations of genes that code for proteins
essential to embryonic development. Embryos that die early miscarry or, in
the case of pregnancies with more than one offspring, may be resorbed back
into the uterus. A 2:1 ration is observed among offspring that develop to term
(normal birth age): two-thirds heterozygotes to one-third homozygous normal
offspring. In mice, for example, the short-tail allele (T’) causes early
embryonic death in the homozygote. The embryo is then resorbed. If such
embryos are taken from the uterus early in pregnancy, before they can be
resorbed, they are seen to have no backbone and none of the mesoderm tissue
normally destined to form the muscles, kidneys, and many other important
organs. Heterozygotes (TT’) have shorter tails than wild-type mice (TT).
Manx cats are heterozygous for a similar lethal allele. The backbone is so
short that the cat has no tail. The last vertebrae of the back and the last part of
the digestive tract may be abnormal, and in this case the cat may have
problems that prevent it from living out a full nine lives.
Characteristics of Molecular Diseases
The reasons: abnormalities in structure of DNA molecule (gene
mutations).
Frequency of occurrence: 1-2 % in human populations. The following
monogenic diseases on the data of McKusick (1988, USA) are known:
● 2106 autosomal dominant;
● 1321 autosomal recessive;
● 276 Х-linked.
There are many polygenic illnesses (diabetes, atherosclerosis, essential
hypertension, schizophrenia, etc.). Their clinical spectrum depends from a
genotype and environment factors (a feed, stresses, the infections, harmful
habits), therefore they are also named as multifactor disease.
Criteria of occurrence frequency:
● high frequency – 1 patient on 10 thousand newborns;
● average frequency – 1: 10 – 40 thousand newborns;
● low frequency – 1: 40 thousand and more.
Classification: it is submitted on the diagram.
Clinical spectrum has a number of features:
1) molecular diseases arise during the different ontogenesis periods (right
after birth, in the early childhood, in pubertal period, but up to
reproductive age).
2) they are characterized by variety of clinical symptoms – polymorphism
(disorders in physical and mental development are observed).
3) they have different degree of pathological current. It is caused by
influence of genes - modifiers and environment factors. As result, at a
similar genotype pathological attributes have various expressivity and
penetrance even among close relatives.
4) they result in the adverse forecast (partial or full invalidity; reduction of
life expectancy);
Diagnostics: biochemical researches (neonatal screening program):
● On Ist stage: there are qualitative reactions (screening-test).
● On IInd stage:
▪ the biochemical analysis (blood, urine, amniotic fluid,
etc.);
▪ microbiological methods;
▪ electrophoresis ;
▪ chromatography;
▪ the radio-immunological analysis.
Treatment: efficiency of treatment depends on terms of disease
diagnosing (if earlier, then better). Treatment has symptomatic character.
MOLECULAR DISEASES
Pathology of structural
proteins
Pathology of fermentative proteins
Pathology of transport
proteins
ENZYMOPATHY
1.
EHLERS –
DANLOS
SYNDROME
IMBALANCE of
aminoacid
exchange–
TYROSINOSES:
1. Phenylketonuria;
2. Alcaptonuria;
3. Albinism
IMBALANCE
of
IMBALANCE
of
carbohydrate
exchange
lipid
exchange
1. Galac tosaemia;
2. Fructosuria
Tay – Sachs
disease
IMBALANCE of
mineral
exchange
Hereditary form
of rickets (hypo-
phosphataemic
rickets)
POLYGENIC– INHERITED DISEASES :
1. pancreatic [insular] diabetes;
2. atherosclerosis;
3. schizophrenia and other.
HAEMOGLO–
BINOPATHY:
∙ SICKLE CELL
AENEMIA;
∙ THALASSAEMIA.
2. WILSON’S
DISEASE
Inborn Errors of Metabolism in Man
Many genes code for proteins that are enzymes for a step in one of the
body’s metabolic pathways. When such a gene mutates, the new code may
produce a defective enzyme unable to carry out its metabolic reaction at a
normal rate. The resulting genetic abnormality is an inborn error of
metabolism. The metabolic disorder of Tay-Sachs disease is lethal, but others
are less severe, and some do little or no apparent harm to affected individuals.
The earliest cases of biochemical mutations were described in man by
A.E. Garrod in 1909 in his book “Inborn Errors of Metabolism”. There are
three important diseases associated with the metabolic breakdown of
phenylalanine. 1) Phenylketonuria is due to accumulation of phenylpyruvic
acid and causes mental disorders. The children suffering with this disease are
known as phenylpyruvic idiots and are unable to break down phenylpyruvic
acid into hydroxyphenylpyruvic acid. 2) Alcaptonuria is due to lack of ability
to break down homogentisic acid into acetoacetic acid. Due to accumulation
of homogentisic acid, the urine of the patients suffering with this disease turns
black as soon as it comes in contact with air. 3) Albinism is due to the
absence of melanin pigment and the individuals suffering with this disease are
incapable of converting dihydroxyphenylalanine into melanin. Another
disease tyrosinosis is also associated with the same metabolic pathway.
Phenylketonuria and albinism are two human hereditary disorders
resulting from defective alleles for enzymes that happen to be on the same
metabolic pathway.
Phenylketonuria
This disease was described by Phelling in 1934.
Synonyms: PKU or Phelling’s disease.
Type of inheritance: autosomal recessive.
The reason: lack the enzyme phenylalanine – 4 – hydrolase.
Population frequency – 1 – 4 sick children : 10 000 newborns.
PKU-affected individuals are homozygous recessives who lack the
enzyme that normally converts the amino acid phenylalanine to another amino
acid, tyrosine. Without this enzyme, phenylalanine builds up, perhaps to 50
times its normal level. Minor metabolic pathways convert some of this
phenylalanine to various other products, such as phenylpyruvic acid, which is
excreted in the urine, giving it a characteristic odor.
High concentrations of phenylalanine and its products inhibit the activity
of many metabolic enzymes. This damages various organs, especially the
brain, and without treatment children with PKU become mentally retarded.
PKU can now be controlled by a special diet low in phenylalanine during
childhood. This prevents most brain damage, but some patients may still have
learning disabilities. Since this treatment must begin within a few weeks of
birth, may state now require that newborns receive a blood test for PKU (and
for several other metabolic disorders). When brain development is complete,
PKU patients can adopt a normal diet.
If a woman homozygous for PKU becomes pregnant, the high
phenylalanine level in her blood is transferred to the fetus through the
placenta. This puts the fetus at risk of mental retardation or microcephaly
(small head). Some such women have returned to a low– phenylalanine diet
during pregnancy, but it is not yet clear whether this eliminates the risks to the
fetus. Since the mother is homozygous for PKU, her children must inherit one
copy of the recessive allele from her. Hence, they will all be PKU carriers (or
homozygotes if they also receive a PKU allele from their father).
Albinism
Type of inheritance: autosomal recessive.
The reason: insufficiency of
enzyme-tyrosinase what
normally converts tyrosine to
melanin.
Population frequency – 1 sick
child : 25. 000 newborns.
Albinism is a condition
characterized by absence of
melanin, the dark pigment that
makes eyes, hair, and skin
brown or black. True albinos
have white hair and very light
skin and eyes. There are two
common types of albinism in
humans. In one form, people
homozygous for a recessive
allele lack an enzyme that
normally converts tyrosine to
melanin.
People with the other common kind of albinism are homozygous recessive for
an abnormal allele of a different gene; these people do make the tyrosine-tomelanin enzyme, but for unknown reasons this enzyme produces almost no
melanin pigment in their bodies. Some marriages between two albino people
have produced normally pigmented children, indicating that one spouse was
homozygous recessive for the first allele, and the other spouse was
homozygous recessive for the second. If both spouses are homozygous
recessive for the same allele, their children are all albino. You may wonder
whether victims of PKU are also albino, since they cannot make the tyrosine
that is eventually converted to melanin. There is no answer, because tyrosine
can be obtained in the diet as well as from conversion of phenylalanine.
However, people homozygous for PKU usually have light coloring because
phenylalanine products inhibit the pigment-forming enzymes. Of course, a
person could be homozygous recessive for both PKU and albinism.
Alcaptonuria
Harrods described this disease in 1902 (England).
Synonyms: black urine disease or ochronosis.
Type of inheritance: autosomal recessive.
The reason: defect in the enzyme homogentisic acid oxidase.
Population frequency – 2 – 5 sick children: 10. 000. 000 newborns.
Alcaptonuria is a rare inherited genetic disorder of tyrosine metabolism.
This is an autosomal recessive trait that is caused by a defect in the enzyme
homogentisic acid oxidase. The enzyme normally breaks down a toxic
tyrosine byproduct, homogentisic acid (also called alkapton), which is
harmful to bones and cartilage and is excreted in urine.
Symptoms: A distinctive characteristic of alkaptonuria is that urine or
earwax exposed to air turns reddish or inky black, depending on what one has
eaten, after several hours because of the build-up of homogentisic acid.
Similarly, urine exposed to air can become dark; this is most obvious in
young children still in diapers. In adulthood, but usually not before age forty,
persons suffering from alkaptonuria develop progressive arthritis (especially
of the spine), due to the long-term buildup of homogentisate in bones and
cartilage.
Diagnosis: Presumptive diagnosis can be made by adding sodium or
potassium hydroxide to urine and observing the formation of a dark brown to
black pigment on the surface layer of urine within 30 minutes to l hour.
Diagnosis can be confirmed by demonstrating the presence of homogentisic
acid in the urine. This may be done by paper chromatography and thin-layer
chromatography. (Seegmiller, 1998).
Treatment: Prevention is not possible and the treatment is aimed at
ameliorating symptoms. Reducing intake of the amino acids phenylalanine
and tyrosine to the minimum required to sustain health (phenylalanine is an
essential amino acid) can help slow the progression of the disease.
Galactosemia
For the first time this disease was described by Royse in 1908.
Type of inheritance: autosomal recessive.
The reason: deficiency or absence of an enzyme Gal-l-PUT .
Population frequency – 1 sick child : 70. 000 newborns.
Galactosemia literally means ‘galactose in the blood’. Galactose is a
sugar, which mainly comes from lactose, the sugar found in milks. Lactose is
normally broken down into the two simple sugars, galactose and glucose. The
galactose is then broken down further and used in many parts of the body
including the brain. In galactosemia it cannon be broken down completely and
used because of deficiency or absence of an enzyme, galactose-l-phosphate
uridyl transferase or Gal-l-PUT. Galactose, galactose-l-phosphate and other
harmful chemicals build up and lead to the serious illness that occurs in the
first few weeks of life once the baby is fed on milk containing lactose. It is a
lifelong condition.
The enzyme is deficient or absent because of a mistake or mutation in the
genetic code, the DNA. Our chromosomes are made of DNA and carry a
coded message rather like a computer program and make us what we are, for
example giving us a particular hair colour.
We have two copies of all our chromosomes (except the sex
chromosomes) and we inherit one copy from our mother and one from our
father. In galactosemia the child inherits a mistake in the area that codes for
the missing enzyme from both parents. The parents are perfectly healthy
because they have one normal gene, which allows them to make enough of
the enzyme to keep them healthy. There is way of knowing that a parent may
carry this disorder until they have an affected child. In each and every
pregnancy there is a 1:4 chance of having another affected baby.
We can look for the genetic mistake (or mutation) in the DNA and when
we do this we find that in quite a high proportion of children there is the same
mutation. We are trying to study whether the mutation is related in any way to
the sorts of problems that children with galactosemia have, but at the moment
there only seems to be a loose association between the mutation and outcome
of affected children.
Galactosemia is rare. In the UK, about l child in 45.000 is born with this
condition so between 12 and 18 children are born each year with it.
Someone with galactosemia is unable to break down and use galactose.
The main dietary source of galactose is lactose, which is found in milks. This
is why the baby becomes unwell, usually in the first week, having appeared
completely normal at birth. Galactose and galactose-l-phosphate levels rise in
the baby’s blood and he or she becomes ill.
Signs of liver disease including jaundice, lethargy, poor feeding and
weight loss are very common. The severity of the liver disease varies a lot.
Babies can also be prone to infection at this stage, although this does not
continue to be a problem. Cataracts may also be present. These symptoms are
not just seen in galactosemia and the pediatrician looking after your baby will
do a range of tests to make the diagnosis.
Once the galactose free diet has been started the liver disease will
disappear and the baby will start to gain weight normally. Over time the
cataracts will also disappear.
Fructosuria
Synonyms: fructose intolerance hereditary, fructosemia.
Type of inheritance: autosomal recessive.
The reason: insufficiency fructose -1- phosphate aldolase.
The minimal diagnostic attributes: anorexia; vomiting; hepatomegaly;
hypoglycemia.
The clinical characteristic: the basic symptoms of fructosemia – disgust
for the food containing fructose (100 %), vomiting (100 %), hepatomegaly
(100 %), a jaundice (100 %) and the spasms caused by hypoglycemia (100
%). Disease is expressed in a suckling after addition in food of fruit juices or
fruit mush and also at early artificial feeding. There is vomiting, persistent
refusal of food. Attributes of hypoglycemia and hypotrophy are developed.
Without treatment children perish on 2-6 month of a life owing to cachexia,
dehydration and hepatic insufficiency.
Diagnostics: Fructosuria, albuminuria, hyper aminoaciduria are found
out at laboratory researches. Fructose loading causes sharp deterioration of a
condition, which results in hyperfructosemia and expressed hypoglycemia.
Fructose-1- phosphate aldolase deficiency in liver, kidneys, mucous of small
intestine lays in a basis of disease.
Treatment: The forecast is favorable at rational diet therapy.
Tay - Sachs Disease
For the first time this disease was described by Tay in 1881 and Sachs in
1887.
Synonyms: amaurosis* idiocy.
Type of inheritance: autosomal recessive.
The reason: lacks the enzyme hexosaminidase, which metabolizes a lipid.
Population frequency – 1: 250. 000 newborns, but in family of East European
Jewish it is more. For instance, population frequency is 1: 5.000 among
Jewish– Ashkenazi, what are born in Poland and Lithuania.
The minimal diagnostic attributes: neuropathy and optic atrophy.
Tay-Sachs disease, a metabolic disorder
resulting in deterioration of the brain and
death by about the age of four, is also the
result of a lethal recessive allele. A
homozygous recessive child lacks the
enzyme
hexosaminidase,
which
metabolizes a lipid in the brain’s nerve
cells. Without this enzyme, the lipid
accumulates and destroys the cells ability
to function. So far, this condition is
untreatable, but genetic tests that detect it
very early in embryonic development are
now widely used. The highest frequency
of this allele occurs among people of East
European Jewish extraction: one in 30
members of this group is a carrier
(heterozygous)
for
this
disorder.
However, about one third of the TaySachs cases in the United States are
among non-Jewish people.
Vitamin D - resistant rickets
Synonyms: family X – linked hypophosphataemia*; phosphate diabetes.
Type of inheritance: X – linked dominant.
The minimal diagnostic attributes: rickets signs, what are not giving in
to treatment by vitamin D; hypophosphataemia*.
The clinical characteristic: hypophosphataemia* is possible to reveal
right after birth. Attributes of rickets appear at the end of the first or the
beginning of the second year of a life when children start to go. Changes of
lower limbs are most expressed as a curvature of long tubular bones. Low
growth, restriction of mobility in large joints (knee, cubital and femoral
articulations), dolichocephalous form of scull and nails dysplasia* are
characteristic. Gait uncertain is typical, but in heavy cases patients cannot go
at all. As against from rickets vitamin D – dependent the common condition
of patients is not broken. Skeletal disorders are less expressed in females.
Diagnostics: in blood the alkaline phosphatase concentration is
increased, but calcium level is norm. Disease is caused by decrease of
reabsorption phosphates in renal tubules.
Ehlers – Danlos syndrome
E. Ehlers in 1901 and H. Danlos in 1908 described it.
Population frequency – 1 : 100 000.
Type of inheritance: autosomal dominant.
The minimal diagnostic attributes: the hyperelastic and fragile skin, the
hypermobile joints, hemorrhagic diathesis.
The clinical characteristic: The Ehlers – Danlos’s syndrome is pathology
of the connective tissue affecting the skin and joints. It differs by types of
inheritance, clinical features and by biochemical defects.
Syndrome is characterized by generalized high mobility of joints and the
expressed extensibility of skin. Vulnerability of skin is increased, therefore,
formation of "cigarette tissue ", keloid scars are typical. There are hypodermic
pseudo-tumors on elbows and knees, on a forward surface of shins –
hypodermic nodules. Vein dilatations are observed. It is possible prematurity
owing to early break of fetal membranes. Fragility of tissues creates
difficulties at surgical intervention. Looseness of joints can lead to muscularskeletal deformations.
Sickle-Cell Anaemia
In humans, the allele responsible for sickle cell anaemia is often lethal in
the homozygous condition. The gene involves codes for the beta (β)
polypeptide chain of haemoglobin, the oxygen-carrying protein found in red
blood cells and responsible for their red color. The sickle allele results from a
point mutation: a change in just one nucleotide pair, which in this case
substitutes valine for glutamic acid as the sixth amino acid in the haemoglobin
beta chain.
This seemingly small change has drastic consequences. Whet red blood
cells containing sickle haemoglobin are exposed to low oxygen levels, the
haemoglobin molecules aggregate and form rigid fibers. These fibers distort
the cells into odd shapes, such as sickles. The sickle cells become stuck in the
capillaries, the narrowest blood vessels, rather than bending and squeezing
through in single file as normal red cells do. The stuck cells impede
circulation to the areas supplied by the blocked capillaries. The sickle cells
also break down easily, leaving the victim with fewer red blood cells than
normal, a condition known as anemia. Poor circulation and anaemia deprive
the tissues of needed oxygen, producing symptoms such as tiredness,
headaches, muscle cramps, poor growth, and eventually perhaps failure of
organs such as the heart and kidneys.
An individual homozygous for a deleterious recessive allele is an
affected individual, whereas a heterozygote is a carrier. People heterozygous
for the sickle allele are sometimes referred to as “having sickle cell trait”.
This phrase is unfortunate, since it suggests that the carrier is less fit than the
normal homozygote, which is not usually the case. The sickle allele occurs
most commonly (but not exclusively) in black people. In the United States,
about l in 400 black newborns is homozygous for the sickle allele.
The sickle and normal alleles are codominant: heterozygotes produce
both normal and sickle beta chains. Their red blood cells sickle only when the
oxygen level is extremely low. For instance, a study showed that black
military recruits who were carriers of sickle cell trait were 28 times more apt
to die from the strenuous exercise of basic training than were homozygous
normal black recruits. Without special blood tests, heterozygotes such as there
may be unaware that they are among the 8% of American black people who
carry the sickle allele.
People homozygous for the sickle allele are more severely affected
because all of their beta chains are abnormal. About half of them die by the
age of 20. Furthermore, women in this group have fewer babies than do
heterozygous or homozygous normal women. We might expect natural
selection to keep such a lethal allele quite rare, because many people
homozygous for the sickle allele die without having children. Yet in large
areas of tropical Africa, 20 to 40% of the people are heterozygous for the
allele. This suggests that heterozygotes have some selective advantage
compared with the normal as well as sickle homozygotes. In 1953 it was
noted that these people lived in the areas with the highest rates of death from
a virulent form of malaria, caused by Plasmodium falciparum, a parasite of
red blood cells.
Having a copy of the sickle allele lowers a person’s chances of
developing malaria. Red blood cells containing sickle haemoglobin sickle
more readily when they are infected with malaria parasites. When a cell
sickles, the parasites inside it die. The body’s defenses may then be able to
destroy the remaining parasites before malaria develops. In malaria infested
regions, therefore, it is advantageous to be heterozygous for the sickle allele,
which protects against a common deadly disease, even though the sickle allele
is usually lethal in the homozygous state.
Sickle-cell anaemia is a blood disease where the red blood cells become
sickle shaped as compared with round shape in normal individuals. This
results into various abnormalities and may ultimately result into death. This
disease is caused by a single gene, which in heterozygous condition causes
moderate sickling (sickle-cell anaemia). It was also found that the
haemoglobin of normal individual and a patient have different mobilities in an
electrophoretic field. Haemoglobin of sickle-cell anaemia moves in a
direction opposite to that of normal haemoglobin. Such a difference was later
discovered (by Ingram in 1957) to be due to the replacement of a single amino
acid in β-chain of haemoglobin
1
2
3
4
5
6
normal haemoglobin
A = val – his – leu – thr – pro – glu – glu
sickle cell haemoglobin
S = val – his – leu – thr – pro – val – glu
In table are segments of β-chains of normal and abnormal haemoglobin
showing amino acid replacement.
Thalassemia
The same explanation may account for the high frequency of
thalassemia, a group of genetic conditions in which too little haemoglobin is
produced, in districts of Italy, Greece, and other areas where malaria was once
common.
So far there are no effective drugs to prevent disease in homozygous
patients. Genetic engineering provides approaches that could help patients
with sickle-cell anaemia or thalassemia. One way is to try to turn on the genes
for gamma (γ) chains of haemoglobin, normally expressed only in the fetus. If
these genes could stay turned on after birth, the gamma chains produced
would combine with alpha (α) chains and form near-normal haemoglobin.
Researchers recently isolated stem cells, which produce all the blood cells,
from bone marrow. If a patient’s stem cells could be isolated, given
transplants of normal beta chain alleles, cultured, and returned to the patient’s
bone marrow, they would provide a lifelong cure. However, these
homozygous patients would still pass on a copy of the sickle or thalassemia
allele to each of their children.
Wilson's disease
For the first time this disease was described by Wilson in 1911 and
N.Konovalov according to clinical disorders called it as hepatocerebral
dystrophy.
Synonyms: Wilson-Konovalov’s disease; hepatocerebral dystrophy,
hepatolenticular degeneration.
Type of inheritance: autosomal recessive.
The reason: ceruloplasmin deficiency, providing copper transport in an
organism.
The minimal diagnostic attributes: the decrease of ceruloplasmin
concentration in plasma; Kaiser-Flasher’s ring on the iris; the increase of the
copper contents in a liver; hepatosplenomegaly; neurological symptoms.
The clinical characteristic: Disease is expressed in the age from 6 till
50 years, but most frequently – in schoolchildren. The first symptoms can be
hepatosplenomegaly, dysfunction of a liver, CNS, sometimes kidneys. Liver
pathology is demonstrated as subacute hepatite with jaundice, vomiting and
dyspepsia. At late stages the cirrhosis and a portal hypertension are
developed. Neurological changes are as dysphagia*, unarticulated speech,
salivation, increased muscular rigidity, hyperkinesias. Decrease in
intelligence, change of behaviour is marked. A specific symptom is a
pigmental green - brown ring on the iris (Kaiser-Flasher’s ring). On autopsy
accumulation of copper in brain, liver, kidneys, spleen, cornea, iris and
crystalline lens are found out.
Diagnostics: the basic biochemical research is detection of ceruloplasmin
deficiency, providing copper transport in an organism. As result the increase
of copper concentration in blood is determined. There are a thrombopenia*, a
leukopenia* and anaemia.
G L O S S A R Y
• Acromegaly – growth of bones and soft tissues of face (enlargement of
a nose, lips, a chin), the increase in sizes of internal organs and limbs.
• Amaurosis – the full blindness.
• Amenorrhea – absence of menses during fertile age.
• Antimongoloid set of the eyes – dropped external angles of palpebral
fissures.
• Aplasia (agenesia) –congenital full absence of organ or its part.
• Arrhinencephaly – aplasia of olfactory bulbs, furrows, tracts and
laminae.
• Ataxy – the loss of coordination in contractions of various muscles
groups at any movements.
• Atresia – the full absence of the ducts or natural foramens in organs.
• Autism – isolation from people, from a life; absorption in the own
world.
• Brachycephaly – short-head person, increased transversal head size
respecting decreased longitudinal size.
• Cataract – eye disease in which basic symptom is turbidity of
crystalline lens.
• Clinodactyly– lateral or a medial curvature of a finger.
• Coarctation – a stenosis (narrowing) of an artery.
• Coloboma – eye absence or defect of any its structure.
• Cryptorchism – the abnormal development of testes, in which testes
don’t descend in scrotum as a result they are located in abdominal cavity or
groin channel.
• Dysphagia – disorder of swallowing.
• Dysplasia - the abnormal embryonic laying and development of tissues
or internal organs.
• Epicanthus – the vertical skin fold near internal corner of an eye
fissure.
• Expressivity – the degree of phenotypical development of the trait
(sign).
• Gynaecomastia – excessive increase of mammary glands in male.
• Haemangioma – a non-malignant growth of blood vessels.
• Hyalinosis – a protein dystrophy kind at which homogeneous,
translucent, dense protein substances are accumulated in tissues between
cells.
• Hydramnion – the superfluous accumulation of amniotic fluid in
amniotic cavity.
• Hydronephrosis – a progressing dilatation of renal canals and renal
pelvis owing to disturbance of urine excretion with the subsequent necrosis of
a kidney tissue.
• Hyperplasia – increase of cells number.
• Hypertelorism – increased distance between organs.
• Hypertrophy – increased of cells volume.
• Hypogenitalism – the abnormally small size of gonads, internal and
external genitals.
• Hypogonadism – decreased gonads.
• Hypophosphataemia – the low concentration of phosphates in
peripheral blood.
• Hypoplasia – the insufficient development of tissues, organs, parts of a
body or the whole organism.
• Hypospadias – the inferior urethra cleft and displacement of urethra
external orifice.
• Hypotelorism – decreased distance between organs (usually about
eyes).
• Hypotonia – decreased tonus of tissues and organs.
• Leukopenia – the low level of leukocytes in peripheral blood.
• Macroclitoris – increased clitoris.
• Macroorchism – enlargement of testes.
• Meningomyelitis – an inflammation of spinal cord substances and its
envelopes.
• Microcephaly – the small sizes of a brain and a brain skull.
• Micrognathia – decreased maxilla.
• Microphthalmia – the small sizes of an eyeball.
• Microstomia – a small oral slit.
• Mongoloid set of the eyes – dropped internal angles of palpebral
fissures.
• Myeloleukemia – a kind of leukaemia at which number of immature
leukocytes (promyelocytes and myelocytes) increases in peripheral blood.
• Osteoporosis – imbalance of a bone tissue structure.
• Otitis – inflammation of a middle ear.
• Penetrance – quantitative index of phenotypical development of the
trait (sign).
• Phenocopy – phenotypical expressions similar to hereditary disease
without changes in genotype.
• Phocomelia – absence [significant lag] of limbs proximal parts. As a
result, foots or hands seem attached directly to a body.
• Polydactyly – increased number of fingers.
• Ptosis – the lowering (usually palpebrae).
• Pylorostenosis – the narrowing of the pylorus.
• Scoliosis – a lateral bending of a backbone.
• Stenosis – the narrowing of the internal organs ducts or orifices.
• Strabismus – a squint [cross-eye].
• Syndactyly– full or partial concretion of the neighbour fingers or toes.
• Synostosis – fused (merged) bones.
• Trigonocephaly – a skull expansion in occipital and the narrowing in a
frontal part.
• Thrombopenia – the low level of thrombocytes in peripheral blood.
B I B L I O G R A P H Y:
1.
2.
3.
4.
5.
6.
С.И.Козлова, Н.С.Демикова, Е.Семанова, О.Е.Блинникова
«Наследственные
синдромы
и
медико-генетическое
консультирование». – Атлас-справочник. – Изд. 2-е дополн. –
М.; Практика, 1996. – 416 стр., 392ил.
A textbooik of cytology, genetics and evolution, ISBN 81-7133161-0, P.K. Gupta (a textbook for university students, published
by Rakesh Kumar Rastogi for Rastogi publications, Shivaji Rood,
Meerut- 250002.
Biology, fourth edition, Karen Arms, Pamela S. Camp, 1995,
Saunders college Publishing.
Intermediate First Year, Zoology: Authors (English Telugu
Versions): Smt. K.Srilatha Devi, Dr. L. Krishna Reddy, Revised
Edition: 2000.
Review Committee, Dr. K. Malla Reddy, Sri Y. Krishnanandam,
Sri B.V.Gopalacharyulu, Sri G.Rama Joga Rao, Teludu Akademi.
Биология/ А.А. Слюсарев, С.В.Жукова. – К.: Вища шк.
Головное изд-во, 1987. – 415 с.
C O N T E N T S:
CHAPTER I: MUTATIONS
Brief history………………………………………………………..…5
Modern classifications of mutations……………………………….…6
Gene mutations………………………………………………….……7
Structural changes in chromosomes……………………………….…8
Numerical changes in chromosomes…………………………..……10
CHAPTER II: HUMAN DISEASES
Hereditary illnesses……………………………………………….…12
Illnesses with hereditary predisposition……………………………..13
Nonhereditary illnesses…………………………………………...…13
CHAPTER III: CHROMOSOMAL SYNDROMES
Total characteristics of chromosomal illnesses……………………...14
Classification of chromosomal diseases………………..…………....16
“Cat-like cry syndrome”………………………………….……..…...16
Translocation form of Down’s syndrome…………………................17
Syndrome of “Philadelphian chromosome”……………………..…..18
Martin –Bell’s syndrome……………………………………….....…19
Syndrome Patau……………………………………………...……....20
Edwards’s syndrome………………………………………………....22
Down’s syndrome………………………………………...……….....23
Syndrome Shereshevskiy- Turner……………………....………........25
Klinefelter’s syndrome………………………………………...….….27
Syndrome of polysomy on the X - chromosome………...…………..28
Syndrome of the additional Y-chromosomes…...…………...…....….29
CHAPTER IY: MOLECULAR DISEASES
Total characteristics of gene diseases…………………….…….……31
Classification of molecular diseases…………………………………32
Phenylketonuria ……………………...……………………………...33
Albinism ………………………………………………………..…...34
Alcaptonuria…………………………………………...…………….35
Galactosemia……………………………………………….………..36
Fructosuria……………………………………...……………………37
Tay-Sachs disease……………………………………………………38
Vitamin D-resistant rickets…………………………………..............38
Ehlers-Danlos syndrome…………………………….…………….....40
Sickle-cell anaemia……………………………..………………....…41
Thalassemia………………………………………………………..…42
Wilson’s disease…………………………………………...................43
GLOSSARY……………….………………………….......44
HEREDITARY DISEASES OF A MAN
Methodological manual for the students
of the English-speaking Medium (on English).
НАСЛЕДСТВЕННЫЕ ЗАБОЛЕВАНИЯ ЧЕЛОВЕКА
Учебное пособие для студентов
англоязычного отделения (на английском языке).
Авторы: Макаренко Элина Николаевна, кандидат медицинских
наук, старший преподаватель кафедры биологии с экологией;
Болдырева Галина Ивановна, старший преподаватель кафедры
биологии с экологией;
Паршинцева Наталья Николаевна, старший преподаватель кафедры
иностранных языков с курсом латинского языка.
Authors: Mackarenko E.N., Senior Lecturers Biology with Ecology of
Department;
Boldyreva G.I., Senior Lecturers Biology with Ecology of Department;
Parshintseva N.N., Teacher of Latin and Foreign Languages Department of
Stavropol State Medical Academy