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Inherited Epidermolysis
Bullosa
Jo-David Fine, M.D.,
M.P.H., Eugene A. Bauer, M.D.,
and Tobias Gedde-Dahl Jr., M.D.
Edited by
Jo-David Fine, M.D., M.P.H., Eugene A. Bauer, M.D. Joseph McGuire, M.D. Alan
Moshell, M.D.
Published in 1999 by The Johns Hopkins University Press. ISBN
0-8018-6024-5
DebRA is grateful to the authors and publishers
for permission to reproduce extracts from this book to make information more widely
available to professionals families and carers.
DIAGNOSTIC TESTS
Junctional EB
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abnormalities in tissue enzymes. In 1984 for example, Kero, Palotie, and Peltonen
identified a few JEB fibroblast cell lines in which collagenase synthesis was elevated.
Similarly, in 1984 and 1985, Manabe and colleagues and Matsumoto and colleagues reported
that the exposure of human skin explants to JEB blister fluid resulted in the production
of intralamina lucida cleavage. As in the case of identical studies in EBS, these findings
were later refuted. In 1986, Heagerty and colleagues demonstrated lack of staining of
Herlitz JEB skin by a monoclonal antibody (GB3) that was later shown to be directed
against the anchoring filament-associated macromolecule, laminin-5, suggesting that this
particular protein might be a target for mutation or injury in JEB. Similar findings were
reported by Fine, Horiguchi, and Couchman in 1989 using a monoclonal antibody
(19-DEJ-1) against a different anchoring filament-associated protein, now named uncein. In
1994, Jonkman and colleagues demonstrated absent staining of bullous pemphigoid antigen-2
(BP- 180; type XVII collagen) in the skin of a patient with the GABEB subtype of JEB. These immunohistochemical studies set the stage for the search for mutations
in the genes encoding for several skin basement membrane proteins, most notably laminin-5
and bullous pemphigoid antigen-2. As early as 1994, Uitto and colleagues demonstrated that
a number of patients with Herlitz and non-Herlitz subtypes of JEB had mutations in the
genes encoding for any of the three chains of laminin-5. In 1995, Vidal and co-workers
demonstrated the presence of mutations in the gene encoding for the a 4 subunit of a 6b 4
integrin, a component of the hemidesmosome, in a patient having JEB in association with
congenital pyloric atresia. In 1996, a few patients with GABEB were shown to have
mutations in the gene for bullous pemphigoid antigen-2, confirming the immunohistochemical
findings by Jonkman in this particular JEB subtype. In 1997, a patient with GABEB was
shown to have mitotic gene conversion of one parental mutation in the gene (COL17A1)
encoding for bullous pemphigoid antigen-2, resulting in reversion of the phenotype in a
mosaic pattern, the first time such a mechanism has been demonstrated in humans. |
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