Epidermolysis Bullosa Simplex in Israel

Background

Epidermolysis bullosa simplex (EBS) is the most common form of epidermolysis bullosa. The disease is characterized by intraepidermal blistering due in most cases to mutations in cytokeratin genes 5 (K5) or 14 (K14). Extensive studies in the United States and Europe have shown that EBS is almost always inherited in an autosomal dominant fashion.

Objective

To assess the possibility that the molecular features of EBS may differ according to the type of population studied.

Design

We assessed 10 Israeli families diagnosed as having EBS and compared their clinical and genetic features with previous observations. Affected individuals underwent complete clinical evaluation. DNA from all family members was assessed for mutations inK5orK14using polymerase chain reaction amplification, direct sequencing, and subsequent mutation verification. In addition, specific cases were genotyped using a panel of microsatellite markers spanning theK14locus.

Results

Eight distinct pathogenic mutations inK5(3 mutations) andK14(5 mutations) were identified. Six of these mutations are novel. The mutations included 2 nonsense mutations and 6 missense mutations. A third of the affected families inherited EBS in a recessive fashion, in contrast with previous observations in Europe and the United States. In addition, we identified a unique case that resulted from compound heterozygosity for a missense and a nonsense mutation inK14. Homozygous nonsense mutations were strongly associated with a severe phenotype.

Conclusion

The present study demonstrates a unique mutation spectrum and a strikingly different pattern of inheritance for EBS in a series of Israeli families compared with families of European or US extraction.