KERATIN-17 MUTATIONS CAUSE EITHER STEATOCYSTOMA MULTIPLEX OR PACHYONYCHIA-CONGENITA TYPE-2

Pachyonychia congenita type 2 (PC-2; Jackson-Lawler syndrome) is an au tosomal dominant disorder characterized by hypertrophic nail dystrophy , mild focal keratoderma, multiple pilosebaceous cysts and other featu res of ectodermal dysplasia, Keratin 17 (K17) is a differentiation-spe cific keratin expressed in the nail bed, hair follicle, sebaceous glan d and other epidermal appendages, Previously, we have demonstrated tha t PC-2 is caused by mutations in K17 and that similar mutations in thi s gene can present as steatocystoma multiplex with little or no nail d ystrophy Here, we describe three unrelated kindreds carrying K17 mutat ions. Two of these families have identical missense mutations (R94C) i n the IA domain of K17, However, while affected members of one kindred have the classical features of PC-2, affected persons in the other fa mily have the steatocystoma multiplex phenotype, In a third family wit h PC-2. mutation N92S was detected, bringing the total number of disti nct mutations reported in K17 thus far to 11, These results demonstrat e that K17 mutations commonly underlie both PC-2 and steatocystoma mul tiplex and that the alternate phenotypes which arise from these geneti c lesions in K17 are independent of the specific mutation involved.