Novel COL7A1 mutations of Hallopeau-Siemens type recessive dystrophic epidermolysis bullosa

Abstract

    Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature termination codon, missense, splice-site mutations on both alleles causes RDEB. In this study, we examined a Japanese EB boy with generalized blistering and scar formation, and made a diagnosis of the Hallopeau-Siemens type RDEB (HS-RDEB), the most severe form of RDEB. Mutational analysis of the COL7A1 gene revealed a novel missense mutation A80P and a novel nonsense mutation Q1211X. In general, HS-RDEB is caused by combination of premature termination codon mutations, but 3 HS-RDEB cases have been reported to have combination of premature termination codon and missense mutations one of which was S48P. This study suggests that even missense mutation, which leads to substitution for proline in amino terminal end of type VII collagen, can cause HS-RDEB.