Dystrophic Epidermolysis Bullosa Inversa with COL7A1 Mutations and Absence of GDA‐J/F3 Protein

Abstract

Epidermolysis bullosa dystrophica inversa (DEB-I) is a very rare disease characterized by autosomal recessive inheritance that causes blistering and erosions on the trunk and extremities occurring in early infancy with a predilection for flexural and mucosal areas thereafter. Ultrastructural findings show dermolytic blistering and absent or rudimentary anchoring fibrils as in generalized forms of dystrophic epidermolysis bullosa. Immunoreactivity for type VII collagen, however, is preserved. We present two patients with DEB-I with compound heterozygosity for the two different COL7A1 mutations, one of them (Arg2069Cys in exon 74) carried by the heterozygous mother, the other one (Lys142Arg in exon 3) carried by the heterozygous father, accompanied by absence of the associated anchoring fibrils protein GDA-J/F3.

An Adult Patient with a Rare Subform of Recessive Dystrophic Epidermolysis Bullosa Inversa (Gedde-Dahl)~!2010-02-28~!2010-04-09~!2010-05-07~!

“…The mutation c.425A>G in exon 3 has been described to lead to abnormal splicing [5], the other mutation, c.6205C>T in exon 74, causes replacement of codon 2069 for arginine by a codon for cysteine. The same molecular constellation of compound heterozygosity has been found in one family before with similar clinical features [6].…”

Pregnancy after PGD for recessive dystrophic epidermolysis bullosa inversa: genetics and preimplantation genetics

“…This confirmed the son's status of compound heterozygote. The inheritance of these mutations was confirmed: the mother carried the c.6205C>T and the father carried the c.425A>G. This mutation combination has been previously reported in RDEB-I [17].…”

“…It represents a cytosine to timine replacement in nucleotide position 6205 of the cDNA. This mutation was described in a DEB inverse, a very rare recessive form occurring in early infancy with preserved immunoreactivity for type VII collagen [17]. This result is compatible with the clinical features of the affected son.…”

“…The main trait is positive staining for type VII collagen at the blister roof and anchoring fibrils are variably reduced and hypoplastic. From the clinical point of view, Kahofer et al [17] described two children with DEB-I with very similar clinical features, in particular congenital blistering on the trunk and extremities shortly after birth and pronounced mucosal involvement. Dental aplasia, nail dystrophy, inguinal blistering, healing with atrophy, and milia were other traits.…”

“…This mutation was screened in the affected child because of his geographical origin (Romania). Finally, the affected son was a compound heterozygote exactly with the same genotype described previously (c.6205C>T/c.425A>G) [17].…”