NOVEL MUTATIONS IN KERATIN-16 GENE UNDERLY FOCAL NON-EPIDERMOLYTIC PALMOPLANTAR KERATODERMA (NEPPK) IN 2 FAMILIES

Keratins K6 and K16 are expressed in suprabasal interfollicular epider mis in wound healing and other pathological conditions associated with hyperproliferation, such as psoriasis and are induced when keratinocy tes are cultured in vitro. However, these keratins are also constituti vely expressed in normal suprabasal mucosal and palmoplantar keratinoc ytes. Mutations in keratins have been reported in the basal keratin pa ir K5 and K14 in epidermolysis bullosa simplex and in suprabasal epide rmal keratins K1, K2 and K10 in epidermolytic ichthyoses. Two families with autosomal dominant disorder of focal non epidermolytic palmoplan tar keratoderma, have oral mucosal and follicular lesions in addition to the palmoplantar hyperkeratosis. Previous studies have shown linkag e in these families to the type I keratin gene cluster at 17q12-q21 an d this report shows that the cDNA of affected members of both families have novel heterozygous mutations in the expressed keratin 16 gene. T hese mutations (R10C and N8S) lie in the helix initiation motif of the 1A domain. These mutations do not appear to cause epidermolysis on li ght or electron microscopy, which may reflect differences in function, assembly or interaction of the 'hyperproliferative' or 'mucoregenerat ive' keratins from other major types of keratins. The mutations report ed here are the first to describe the molecular pathology of focal non epidermolytic palmoplantar keratoderma.