title: A novel mutation and large size polymorphism affecting the V2 domain of keratin 1 in an African-American family with severe, diffuse palmoplantar keratoderma of the ichthyosis hystrix Curth-Macklin type.
abstract: Keratin gene mutations affecting nonhelical head and tail domains are not usually associated with prominent skin blistering and keratin filament clumping. Instead, they have been associated with several distinct clinical phenotypes, such as epidermolysis bullosa simplex with mottled pigmentation (mutation P25L in the V1 domain of keratin 5), epidermolysis bullosa simplex with migratory circinate erythema (frameshift mutation c1649delG in the V2 domain of keratin 5), striate palmoplantar keratoderma (PPK), and ichthyosis hystrix Curth-Macklin (different frameshift mutations in the V2 domain of keratin 1 (K1)). We have studied a family with severe, diffuse, nonepidermolytic PPK and verrucous hyperkeratotic plaques over the joints and in flexures and identified a new KRT1 gene mutation that is predicted to completely alter the K1 tail domain. In addition, a new K1 size polymorphism has been detected, which is especially prevalent among the African-American population. These results further emphasize the functional importance of the nonhelical tail domain in keratin molecules despite the obvious variability in the number of glycine loop motifs and underscore the broad phenotypic spectrum of disorders due to dominant keratin tail mutations.
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Richardson
authors.forename: Jason B
authors.initials: JB
authors.lastname: Lee
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Hyde
authors.forename: Gabriele
authors.initials: G
authors.lastname: Richard
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D053556:Keratin-1; D007633:Keratins / Q000235:genetics*; D015776:Keratoderma, Palmoplantar, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion
chemical_list: C491616:KRT1 protein, human; D053556:Keratin-1; D007633:Keratins; D005998:Glycine