Human Nidogen Gene: Identification of Multiple RFLP and Exclusion as Candidate Gene in a Family with Epidermolysis Bullosa (EBS2) with Evidence for Linkage to Chromosome 1

Epidermolysis bullosa (EB) is a group of heritable blistering diseases affecting the dermal-epidermal basement membrane zone. We have recently provided evidence for genetic linkage of the molecular defect in a large family with dominant simplex, generalized (Koebner) type of EB (EBS2) to the long arm of chromosome 1. Because human nidogen gene has been mapped to chromosomal locus 1q43 in the human genome, we examined the possibility that nidogen, an integral component of all basement membranes, would be the candidate gene in this family of EBS2. Restriction fragment- length polymorphism, which was shown with several restriction endonucleases to be present within the nidogen gene, was utilized for linkage analyses. The results using an informative PvuII polymorphism as a marker of allelic inheritance supported exclusion of the EBS2 locus from approximately 10 cM in either side of the nidogen locus, when Lod score of -2.0 was taken as the limit of exclusion. This study demonstrates the feasibility of examining other families with EB for possible linkage to the nidogen locus.