PARTIAL DOMINANCE OF A KERATIN-14 MUTATION IN EPIDERMOLYSIS-BULLOSA SIMPLEX - INCREASED SEVERITY OF DISEASE IN A HOMOZYGOTE

Epidermolysis bullosa simplex is a disease in which keratin gene mutat ions cause the production of defective intermediate filaments, which l eads in turn to epidermal basal cell fragility and blistering. The inh eritance in nearly all kindreds is autosomal dominant, most kindreds h ave missense mutations, and the encoded proteins appear to exert a dom inant negative function. One previously reported patient with generali zed blistering had a fully dominant mutation of keratin 5; in that kin dred a homozygote was affected no more severely than the heterozygotes . By contrast we report-here a keratin 14 mutation that causes blister ing limited to the hands and feet in heterozygotes, but homozygotes ha ve more severe, widespread blistering of the skin and mucous membranes . Thus keratin gene mutations may be not only fully recessive or fully dominant but also partially dominant as well.