title: Identification of sporadic mutations in the helix initiation motif of keratin 6 in two pachyonychia congenita patients: further evidence for a mutational hot spot.
abstract: Pachyonychia congenita (PC) is a rare, autosomal dominant, ectodermal dysplasia characterized most distinctly by the presence of symmetric nail hypertrophy. In the Jadassohn-Lewandowsky form, or PC-1, additional cutaneous manifestations may include palmoplantar hyperkeratosis, hyperhidrosis, follicular keratoses, and oral leukokeratosis. Mutations have previously been identified in the 1A helix initiation motif of either keratin 6 or keratin 16 in patients with PC-1. In the current study, we have identified 2 sporadic, heterozygous mutations in the 1A helix region of the K6 isoform (K6a). The first mutation identified was a 3 base pair deletion (K6adelta N171). The second mutation was a C-to-A transversion resulting in an amino acid substitution (K6a N171K). These data, in combination with previous reports, provide further evidence that this location is a mutational hot spot.
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Lin
authors.forename: M L
authors.initials: ML
authors.lastname: Levy
authors.forename: P E
authors.initials: PE
authors.lastname: Bowden
authors.forename: C
authors.initials: C
authors.lastname: Magro
authors.forename: L
authors.initials: L
authors.lastname: Baden
authors.forename: H P
authors.initials: HP
authors.lastname: Baden
authors.forename: D R
authors.initials: DR
authors.lastname: Roop
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D004247:DNA / Q000097:blood; D017931:DNA Primers; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007633:Keratins / Q000737:chemistry / Q000235:genetics*; D008297:Male; D009264:Nails, Malformed / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D012871:Skin Diseases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D007633:Keratins; D004247:DNA