A novel homozygous point mutation in the COL17A1 gene in a Chinese family with generalized atrophic benign epidermolysis bullosa

We describe a Chinese family with generalized atrophic benign epidermolysis bullosa (GABEB), a non-lethal variant of junctional epidermolysis bullosa. The proband was an offspring of consanguineous parents, had generalized blisters since birth and developed severe alopecia during early childhood. Ultrastructural examination of the proband's skin revealed fissures in the lamina lucida. Immunofluorescence assays using a monoclonal antibody recognizing the extracellular domain of the 180 kDa bullous pemphigoid antigen (BPAG2) showed loss of fluorescent signal in the basal membrane zone of the skin. DNA sequencing revealed a homozygous C-to-G transversion at nucleotide position 899 in exon 11 of the COL17A1 gene, which encodes BPAG2. This mutation results in serine to cysteine at position 265, which is located in a highly conserved region of the intracellular domain of BPAG2. We showed that the proband's father was heterozygous for this mutation. In addition, we found a novel polymorphic substitution of C-to-G at nucleotide position 798 in exon 10 of the COL17A1 gene, which results in an I233M change in BPAG2 and is a common polymorphic allele in a limited Chinese population.