Download - Abdel Hamid Derm Atlas

Inherited epidermolysis bullosa
Gap Junctions
•
Epithelial cells use hemidesmosomes
as way of attaching to the connective
tissue Hemidesmosomes are
responsible for attaching epithelial
cells to the basement membrane
which maintains cell integrity.
Hemidesmosomes are involved in
signal transduction and assist in the
organisation of the cytoskeleton,
apoptosis, and differentiation.
• Epidermolysis Bullosa
Defects in hemidesmosomal proteins
can lead to blistering diseases of the
skin
Inheritance, salient clinical features and differential diagnosis of
the major
subtypes of epidermolysis bullosa
The gene that causes this disease is located on chromosome 8. The specific locus is 8q24 from base pair 144,989,320 to base pair 145,040,912 on the long arm
band.
classification of inherited epidermolysis bullosa
Common types of epidermolysis bullosa and target
proteins IJDVL 78 : 692, 2O12
Inherited epidermolysis bullosa
An. Brasil. Dermat. 88 no. 2 ,2O13
Medecine: 2OO8
Schematic representation of the cutaneous basement membrane
zone. On the right, the approximate levels of tissue separation in four
different variants of epidermolysis bullosa (EB) are indicated.J. Invt. Derm 123
no 1O, 2OO4
Schematic of the skin basement membrane zone. Components in red
characters are target proteins of basal EBS.
Schematic of desmosomes. Components in red characters
are target proteins of suprabasal EBS
JAAD 7O : 11O3, 2O14
•
. The
scheme depicts the cell layers of the epidermis,
the basal keratinocytes, and above them the
suprabasal keratinocyte layers (spinous and granular
layers), which are covered by the horny layer (pink).
The epidermis is attached to the dermis by the
bilayered basement membrane consisting of lamina
lucida and lamina densa (red bar). On the left, the
level of blister formation is indicated. In EB simplex
(EBS) suprabasal, the blisters form within the
middle/upper epidermal layers, depending on which
protein is mutated. In EBS basal, the cleavage plain
is within the basal keratinocytes. In junctional EB
(JEB), the separation takes place within the lamina
lucida, and in dystrophic EB (DEB), within the
sublamina densa region within the uppermost
dermis. In Kindler syndrome (KS), cleavage can
occur within the basal keratinocytes, at the level of
the lamina lucida or below the lamina densa. On the
right, the localizations of the relevant mutated
proteins are indicated. Transglutaminase 5 is present
in the uppermost cell layers of the epidermis.
Plakoglobin and desmoplakin are desmosomal
proteins that are panepidermal, compared with
plakophilin 1, which is expressed mainly in the
suprabasal epidermis. Keratins 5 and 14, plectin,
BP230, exophilin 5 and kindlin-1 are found mainly
within the basal keratinocytes. Integrin α6β4, integrin
α3, and collagen XVII are transmembrane proteins
with extracellular domains emanating from the
plasma membrane of the basal keratinocytes into the
lamina lucida. Laminin 332 is a lamina lucida protein
and collagen VII, the major component of the
anchoring fibrils, is found in the sublamina densa
region.
Electron micrograph of cutaneous basement membrane zone (a) and
schematic illustration of molecular components which are involved in
different form of EB (b) IJDVL 78:692, 2O12
•
•
Complexity of the cutaneous basement membrane zone and molecular-based
classification of epidermolysis bullosa. The figure schematically depicts basal
keratinocytes at the lower part of the epidermis, separated from the papillary dermis
by a dermal-epidermal basement membrane. Ultrastructurally recognizable
attachment complexes and structural components of the basement membrane zone
are indicated on the left, while specific proteins localized within each layer are
indicated on the right. The level of tissue separation within each subgroup of
epidermolysis bullosa is shown on the right. Acta Dermato venerelogica 89:228, 2OO9 .
Appearance of lesions in patients with junctional epidermolysis bullosa
An. Brasil. Dermat. 88 : no.2, 2O13
Appearance of lesions in patients with dystrophic epidermolysis bullosa
An. Brasil Derm. 88: no. 2, 2O13
Epidermolysis bullosa
Epidermolysis bullosa
Recessive dystrophic epidermolysis bullosa
Immunofluorescence mapping technique
IJDVL 78 : 692, 2O12
An Brasil Derm. 85: nO. 6 , 2O1O
An Brasil Derm. 85: nO. 6 , 2O1O
An Brasil Derm. 85: nO. 6 , 2O1O
An Brasil Derm. 85: nO. 6 , 2O1O
Photomicrograph showing normal expression of laminin 332 in the control skin
and complete absence of staining in JEB-H (a and b, respectively) and normal
expression of type VII in the control skin and complete absence of staining in
RDEB (c and d, respectively) IJDVL 78 : 692, 2O12
•
Clinical features and molecular analysis in a family with epidermolysis bullosa simplex. (a) Severe and widespread blistering in patient III-1. (b)
Sequence analysis reveals a heterozygous G>A at complementary DNA (cDNA) position 1163 of the KRT14 gene in the proband (upper panel) and his
asymptomatic father (middle panel) resulting in p.R388H substitution, as well as a heterozygous T>C transition at cDNA position 548 of the KRT5 gene
resulting in p.I183T substitution in the proband (upper panel) and his mother (lower panel); the p.I183T and p.R388H are marked with an arrow. (c) To
confirm segregation of mutation p.I183T with the disease in the family, a 259-bp-long PCR-amplified DNA fragment (forward primer 5′CAAATCGACCCCAGCATCCA-3′; reverse primer 5′-CAGTCTAATTCAGAACGTGTCC-3′) was digested overnight at 65 °C with DNA endonuclease
TaqαI: carriers of the mutation display a 259-bp fragment, whereas noncarriers show a 176-bp fragment only. To confirm segregation of mutation
p.R388H with the disease in the family, we used a PCR–restriction fragment length polymorphism assay previously described (Ciubotaru et al., 2003;
Abu Sa’d et al., 2006). (d) Conseq analysis attributes a maximal conservation score to residue I183 (http://conseq.tau.ac.il/). I183 is marked with an
arrow J. Investigative Derm 132:2852, 2O12.