MITOCHONDRIAL A7445G MUTATION IN 2 PEDIGREES WITH PALMOPLANTAR KERATODERMA AND DEAFNESS

New Zealand and a Scottish pedigree with maternally inherited sensorin eural deafness were both previously shown to carry a heteroplasmic A74 45G mutation in the mitochondrial genome, More detailed clinical exami nation of the New Zealand family showed that the hearing loss was prog ressive, with the severity of the overall loss and the frequencies mos t affected differing markedly between individuals of similar age, and showed that many relatives also had palmoplantar keratoderma, Review o f the literature demonstrated three other large families with presumed autosomal dominant inheritance of palmoplantar keratoderma and hearin g loss, In a United Kingdom pedigree the syndrome was transmitted by f emale and male parents, an inheritance pattern which made mitochondria l inheritance unlikely; however, in a Turkish and a Japanese pedigree the affected individuals were all maternally related, Subsequent analy sis of the Japanese pedigree documented the same A7445G mitochondrial mutation as was previously found in the New Zealand and Scottish pedig rees, Other mitochondrial sequence variants previously reported in the New Zealand or Scottish pedigrees were absent from the Japanese pedig ree which suggests that the A7445G; mutation arose independently in al l three pedigrees, To our knowledge palmoplantar keratoderma has not p reviously been associated with mitochondrial defects; however, the cur rent findings suggest that the A7445G mutation is associated not only with progressive hearing loss but also with palmoplantar keratoderma, The penetrance and expressivity of both symptoms varied considerably b etween individuals in the Scottish and New Zealand Studies which sugge sts that additional environmental and/or genetic factors are involved. (C) 1998 Wiley-Liss, Inc.