Inherited epidermolysis bullosa

1. Inherited epidermolysis bullosa

3. 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 BullosaDefects in hemidesmosomal proteins can lead to blistering diseases of the skin Gap Junctions

4. 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.

5. classification of inherited epidermolysis bullosa

7. Common types of epidermolysis bullosa and target proteins IJDVL 78 : 692, 2O12

8. Inherited epidermolysis bullosaAn. Brasil. Dermat. 88 no. 2 ,2O13

9. Medecine: 2OO8

11. 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

12. Schematic of the skin basementmembrane zone. Components in red characters are target proteins of basal EBS.

13. Schematic of desmosomes. Components in red characters are target proteins of suprabasal EBS

14. . 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. JAAD 7O : 11O3, 2O14

15. 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

16. 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 .

20. Appearance of lesions in patients with junctional epidermolysis bullosa An. Brasil. Dermat. 88 : no.2, 2O13

21. Appearance of lesions in patients with dystrophic epidermolysis bullosaAn. Brasil Derm. 88: no. 2, 2O13

22. Epidermolysis bullosa

23. Epidermolysis bullosa

24. Recessive dystrophic epidermolysis bullosa

25. Immunofluorescence mapping techniqueIJDVL 78 : 692, 2O12

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28. An Brasil Derm. 85: nO. 6 , 2O1O

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30. 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

32. 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.