title: Novel mutations in keratin 16 gene underly focal non-epidermolytic palmoplantar keratoderma (NEPPK) in two families.
abstract: Keratins K6 and K16 are expressed in suprabasal interfollicular epidermis in wound healing and other pathological conditions associated with hyperproliferation, such as psoriasis and are induced when keratinocytes are cultured in vitro. However, these keratins are also constitutively expressed in normal suprabasal mucosal and palmoplantar keratinocytes. Mutations in keratins have been reported in the basal keratin pair K5 and K14 in epidermolysis bullosa simplex and in suprabasal epidermal keratins K1, K2 and K10 in epidermolytic ichthyoses. Two families with autosomal dominant disorder of focal non epidermolytic palmoplantar keratoderma, have oral mucosal and follicular lesions in addition to the palmoplantar hyperkeratosis. Previous studies have shown linkage in these families to the type I keratin gene cluster at 17q12-q21 and this report shows that the cDNA of affected members of both families have novel heterozygous mutations in the expressed keratin 16 gene. These mutations (R10C and N8S) lie in the helix initiation motif of the 1A domain. These mutations do not appear to cause epidermolysis on light or electron microscopy, which may reflect differences in function, assembly or interaction of the 'hyperproliferative' or 'mucoregenerative' keratins from other major types of keratins. The mutations reported here are the first to describe the molecular pathology of focal non epidermolytic palmoplantar keratoderma.
authors.affiliation: Experimental Dermatology Research Laboratory, London Hospital Medical College, UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Shamsher
authors.forename: H A
authors.initials: HA
authors.lastname: Navsaria
authors.forename: H P
authors.initials: HP
authors.lastname: Stevens
authors.forename: R C
authors.initials: RC
authors.lastname: Ratnavel
authors.forename: P E
authors.initials: PE
authors.lastname: Purkis
authors.forename: D P
authors.initials: DP
authors.lastname: Kelsell
authors.forename: W H
authors.initials: WH
authors.lastname: McLean
authors.forename: L J
authors.initials: LJ
authors.lastname: Cook
authors.forename: W A
authors.initials: WA
authors.lastname: Griffiths
authors.forename: S
authors.initials: S
authors.lastname: Gschmeissner
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D005810:Multigene Family; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: D017931:DNA Primers; D007633:Keratins; C027908:endodeoxyribonuclease DdeI; D015252:Deoxyribonucleases, Type II Site-Specific