Inherited palmoplantar keratoderma and sensorineural deafness associated with A7445G point mutation in the mitochondrial genome

We report a French pedigree with members having an inherited combination of non-epidermolytic palmoplantar keratoderma (NEPPK) and sensorineural deafn ess. The penetrance of both features was incomplete. Additional ectodermal defects were absent. The expression of numerous epidermal proteins (keratin s, fillagrin, cornified envelope proteins, intercellular junction proteins including connexin 26, and loricrin) defined with immunolabelling was norma l in the proband. The combination was shown to be associated with the A7445 G point mutation in the mitochondrial genome (mtDNA). This mutation is resp onsible for a subtype of NEPPK which is so far the only mtDNA mutation-asso ciated keratoderma.