Genetic linkage analysis of epidermolysis bullosa simplex, Köbner type

Abstract

Genetic linkage relationships between a range of marker loci and the locus for epidermolysis bullosa simplex (EBS), Köbner type, were examined in a single kindred. A positive lod score of 1.2 at theta = 0.2 was found for Fy. To test the clinical observation that Köbner and Weber-Cockayne types may be the same disease determined by different alleles, published lod scores from definite Weber-Cockayne families were added to those from this study. A lod score of 1.8 was found at theta = 0.2. This value falls to 1.5 at theta = 0.2 when all families other than Ogna type are included. The Köbner variant studied is not closely linked to GPT and is therefore distinct from EBS1 (Ogna type). Linkage analysis is consistent with an hypothesis that Köbner and Weber-Cockayne types are determined by a single locus; however, further evidence is needed before this locus can be designated EBS2 and assigned to chromosome 1.

Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils.

“…Previous linkage analyses have suggested the presence of the mutated locus on the long arm of chromosome 1 in some families with the simplex form of EB (EBS) (28,29). Furthermore, a strong genetic linkage to the GPT locus on chromosome 8 has been demonstrated in a family with the rare Ogna variant of EBS (30).…”

Report of the committee on the genetic constitution of chromosomes 1 and 2

“…Pooled data from families with Kobner and Weber-Cockayne types of Epidermolysis bullosa simplex give a lod score with FY of 1.8 at e=0.2 (Mulley et al 1984). Further evidence is clearly needed before an assignment can be made.…”

A mutation (met→arg) in the type I keratin (K14) gene responsible for autosomal dominant epidermolysis bullosa simplex

“…The disease appears to be fully penetrant and clinical details have been reported (Humphries et al, 1990). In previous studies of a number of families, tentative genetic linkage to the Duffy (Fy) blood group locus has been obtained (Hauge, 1962;Mulley et al, 1984;Humphries et al, 1990). In addition, a family with the "Ogna" variety of the dominant simplex form of the disease has been mapped on chromosome 8q to the enzyme marker glutamic-pyruvic transaminase (GPT) with a lod score of 10.98 at 5 cM (Olaisen and Gedde-Dahl, 1973).…”