Download Carrier Screening

Leslie Ordal, MSc. in Genetic Counselling, candidate, Clinical Genetics Department, Hospital for Sick Kids, Toronto, ON
Feature
Carrier Screening
G
enetic diseases can occur among
people of all backgrounds, but
some genetic disorders occur
more frequently in certain ethnic
groups. Screening is offered to individuals or couples on the basis of their ethnic
background to see if they are at a higher risk
of having a child with one of these genetic
conditions. Some conditions screened for
are more common and have available treatments, such as sickle cell disease, while others are rare enough to fall into the category
of orphan diseases. In Ontario, screening for
several orphan diseases is offered to individuals of Ashkenazi Jewish heritage. The conditions selected for screening are either more
likely to occur in this population or there
is a common mutation in this group that is
easily tested. The orphan diseases currently
covered are Tay-Sachs disease, Canavan disease, mucolipidosis (type IV), familial dysautonomia, Niemann-Pick disease (types A
and B), Bloom syndrome, and Fanconi anemia (group C).
Humans have about 30,000 genes, which
act as instructions to tell the body how to
grow and function. Everyone has two copies
of each gene - one copy is inherited from each
parent. If a gene has a mutation (a change
that causes it not to work properly), this can
result in a medical condition. The conditions
targeted by ethnicity-based carrier screening
are recessive, meaning there must be mutations in both copies of a gene to cause the
disease. A person with a mutation in only one
copy is called a carrier, meaning they do not
show symptoms of the disease but can pass
the mutation on to their children.
Everyone is a carrier of an estimated
6-10 recessive conditions, but this does not
typically pose a risk to their health. If, however, two parents carry a mutation in the
same gene, there is a 25% chance for each
child to inherit both mutations and therefore
have the genetic condition. Ethnicity-based
carrier screening aims to identify couples at
a higher risk of carrying the same genetic
condition due to being members of the same
ethnic group. They can then be offered information and additional testing to help
make the family planning decisions that are
right for them. Carrier screening is often
ADVOCATE, Volume 20/Issue 2 Summer 2013
offered in the context of prenatal care, but
it is ideally done pre-conception. Annual
screening clinics, such as those at Mount
Sinai Hospital in Toronto, for example, exist to raise awareness and give people with
Ashkenazi Jewish heritage the chance to be
screened at any point during their reproductive life.
For an individual who is found to be a
carrier of a recessive genetic condition,
testing is offered to their partner. If both
partners are found to be carriers of the
same condition, they are usually referred
for genetic counselling to receive support
and learn more about their options, which
may vary depending on whether they are
currently pregnant. One option is to have
no additional testing. Another option is
prenatal diagnosis, where chorionic villus
sampling (CVS) or amniocentesis is used to
see if the fetus is affected with the genetic
support about their new child’s medical
needs. Unfortunately, as with most orphan
diseases, highly effective treatments are
not yet available for the orphan diseases
targeted through ethnicity-based carrier
screening in Ontario. Treatments for this
group of diseases are largely supportive and
symptom-based. Tay-Sachs disease causes
progressive damage to the nervous system,
often beginning with seizures and loss of
motor control and eventually leading to difficulties in swallowing and breathing. Most
affected children do not live past the age of
four. Canavan disease is also characterized
by neurodegeneration that begins in infancy, with life expectancy varying from childhood to the early 20’s. Mucolipidosis (type
IV) is caused by the abnormal accumulation
of lipids in the lysosomes, leading to vision
problems, progressive loss of motor control,
and intellectual disability. Familial dysauto-
The conditions targeted by ethnicity-based carrier screening are
recessive, meaning there must be mutations in both copies of a
gene to cause the disease.
condition in question. These tests provide
high diagnostic accuracy but come with an
increased risk of miscarriage. Parents of an
affected fetus have the option to continue or
end the pregnancy. This is a highly personal
and often difficult decision, but families are
supported in whatever choice they make.
Another option is preimplantation genetic
diagnosis, or PGD, which uses in vitro fertilization (IVF) technology to create embryos that are tested for the genetic condition
before implantation. PGD is not covered by
OHIP and is therefore less commonly used
than prenatal diagnosis methods. Additionally, issues such as what to do with affected
and other non-implanted embryos - which
may be stored indefinitely, discarded, donated to others experiencing infertility, or
used for research purposes - may have an
impact on some families’ decision to use
PGD technology.
Parents who choose to continue an affected pregnancy are given guidance and
nomia affects the development and survival
of certain nerves. Symptoms such as impaired blood pressure and body temperature
regulation may be present at birth, with poor
motor control and developmental delay also
often occurring. Niemann-Pick disease type
A presents in infancy with spleen and liver
problems and rapid neurogeneration, with a
life span of around 3 years. Niemann-Pick
type B is typically milder and more variable in its symptoms; affected individuals
may live into adulthood. Bloom syndrome
causes problems with growth, an increased
susceptibility to certain infections, and a
higher risk of developing cancer. Fanconi
anemia can also cause immunodeficiency
and a higher cancer risk, along with additional health problems.
In some places, such as in some areas
of the U.S., carrier screening for multiple
orphan diseases – as well as more common
Continued on page 6
5
Robert Scheuermann, MLT, BSc., MBA/HCM
Getting To Know District 6
High quality
laboratory services
D
istrict 6 spans a collection of 9
counties and/or regional municipalities in Southwestern
Ontario, which includes Wentworth, Brant, Halton, Waterloo, Perth, Wellington, Dufferin, Grey, and Bruce counties.
These areas are beautiful with some breathtaking views extending along the Niagara
escarpment through Hamilton to the tip of
the Bruce Peninsula. More than 2 million
people reside in the 20,000 km2 expanse
that makes up the areas of District 6.
There are many great laboratory minds
and leaders within the boundaries of District 6. The laboratory services therein
range from small rural health labs to moderately-sized healthcare facilities to state
of the art, internationally-recognized, academic centres of excellence.
countryside a few short hours from Toronto
and the U.S. – a destination internationally
renowned as one of North America’s great
arts towns.” (http://www.visitstratford.ca/)
To the southeast is the city of Brantford, which is well known to be the Canadian home of Alexander Graham Bell and
Wayne Gretzky. Moreover, the Brantford
Community Healthcare System (BCHS),
a leader in healthcare and laboratory technology, became the home of “Canada’s
first automated laboratory” in 2011.
“This is the first time chemistry, immunochemistry, hematology and coagulation
have been automated into a single integrated system, said Don Manning, director of laboratory and diagnostic imaging.
“It improves patient safety and it improves
patient care because the tests needed for
There is much world-renown testing and research being conducted at the Hamilton hospitals and McMaster University in the
laboratory disciplines of genetics, chemistry, immunology, hematology, and pathology with exciting achievements.
Stratford is the main laboratory services
hub of the Inter-Hospital Laboratory Partnership (IHLP), a partnership of 12 rural/
community hospital laboratory services.
Seven of the twelve IHLP medical laboratories are situated within District 6 and
provide high quality laboratory services for
a large geographical area. “Few places in
Ontario are lovelier or more alive with culture and character than Stratford. We are a
charming Victorian city nestled in pastoral
diagnosis can be done much more quickly,” said Dr. Kathy Chorneyko, the laboratory’s medical director. “A faster test result
means quicker diagnosis and treatment
for the patient.” (http://www.brantfordexpositor.ca/2011/02/04/bgh-opens-canadasfirst-automated-laboratory)
The home of the Hamilton Regional
Laboratory Medicine Program (HRLMP)
is less than thirty minutes down Highway
403 from Brantford in the City of Hamil-
Feature continued from page 5
likely the result of both the recognition that
many people have diverse ancestry and the
rapidly falling cost of genetic testing in
general. It will be interesting to see if similar changes take place in Ontario and else-
conditions, such as sickle cell and other
hemoglobinopathies – is increasingly being offered regardless of ethnicity. This is
6
ton. The HRLMP is a collaborative program of Hamilton Health Sciences Centre,
St. Joseph’s Healthcare and McMaster
University and is the main academic hub
for laboratory medicine in District 6. There
is much world-renown testing and research
being conducted at the Hamilton hospitals
and McMaster University in the laboratory
disciplines of genetics, chemistry, immunology, hematology, and pathology with
exciting achievements.
“A team of scientists at McMaster
University has discovered the drug, thioridazine, successfully kills cancer stem
cells in the human while avoiding the toxic
side-effects of conventional cancer treatments.” The unusual aspect of our finding
is the way this human-ready drug actually
kills cancer stem cells; by changing them
into cells that are non-cancerous,” said
Mick Bhatia, the principal investigator for
the study and scientific director of McMaster’s Stem Cell and Cancer Research Institute (SCC-RI) in the Michael G. DeGroote
School of Medicine. (http://fhs.mcmaster.
ca/main/news/news_2012/targeting_human_cancer_stem_cells.html)
There are many great laboratory professionals in the district that provide
never-ending passion, knowledge, and
experience to academic teaching centres,
medical laboratory research and laboratory
diagnostic support services to the benefit
of more than 2 million Ontarians. This is
just a fractional snapshot of the amazing
work that laboratory professionals do in
District 6 and throughout the Province of
Ontario. ❖
where in Canada given the great advances
taking place in genetic testing technology,
as well as the increasing focus on, and
awareness of, orphan diseases. ❖
ADVOCATE, Volume 20/Issue 2 Summer 2013