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Epidermolysis Bullosa Simplex in Israel
Clinical and Genetic Features
Dan Ciubotaru, MD;
Reuven Bergman, MD;
David Baty, PhD;
Margarita Indelman, MSc;
Ellen Pfendner, PhD;
Danny Petronius, MD;
Hannah Moualem, RN;
Moien Kanaan, PhD;
Danny Ben Amitai, MD;
W. H. Irwin McLean, PhD;
Jouni Uitto, MD, PhD;
Eli Sprecher, MD, PhD
Arch Dermatol. 2003;139:498-505.
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 in K5 or K14 using polymerase chain reaction amplification, direct sequencing, and subsequent mutation verification. In addition, specific cases were genotyped using a panel of microsatellite markers spanning the K14 locus.
Results Eight distinct pathogenic mutations in K5 (3 mutations) and K14 (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 in K14. 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.
From The Gunther Kahn Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel (Drs Ciubotaru, Bergman, Petronius, and Sprecher and Mss Indelman and Moualem); Human Genetics Unit, Ninewells Hospital, Dundee, Scotland (Drs Baty and McLean); Department of Dermatology and Cutaneous Biology and Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pa (Drs Pfendner and Uitto); Department of Life Sciences, Bethlehem University, The Palestinian Authority (Dr Kanaan); and Pediatric Dermatology Unit, Rabin Medical Center, Petach-Tikvah, Israel (Dr Amitai). The authors have no relevant financial interest in this article.
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ABSTRACT
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