A DELETION MUTATION IN COL17A1 IN 5 AUSTRIAN FAMILIES WITH GENERALIZED ATROPHIC BENIGN EPIDERMOLYSIS-BULLOSA REPRESENTS PROPAGATION OF AN ANCESTRAL ALLELE

Patients with generalized atrophic benign epidermolysis bullosa, a usu ally nonlethal form of junctional epidermolysis bullosa, have generali zed blistering, nail dystrophy, patchy alopecia, and dental abnormalit ies, Skin fragility in most cases is due to mutations in the gene enco ding type XVII collagen (COL17A1), Recently, we reported five Austrian families with generalized atrophic benign epidermolysis bullosa who s hare the same COL17A1 mutation, Affected individuals in three families are homozygous for 4003delTC, whereas those in two others are compoun d heterozygotes, To determine if the occurrence of 4003delTC in these unrelated families signifies propagation of an ancestral allele or a m utational hot spat, haplotypes were determined for polymorphisms both within and flanking COL17A1, Fire intragenic polymorphisms were chosen based on their informativeness, One of these, not previously reported , was 2988 A or C that introduces a new restriction site for Eco0109 I . All the 4003delTC alleles showed the same haplotype for these five p olymorphic markers, Fourteen microsatellite polymorphisms were selecte d based on their high heterozygosity and their location within 10q23-q 25 near COL17A1. Three families shared microsatellite polymorphisms co vering at most 19 cM, whereas the others shared smaller regions consis tent with cross-over events during passage of this mutation through se veral generations, These results indicate that 4003delTC occurs on a s ingle ancestral allele.