title: A heterozygous frameshift mutation in the V1 domain of keratin 5 in a family with Dowling-Degos disease.
abstract: Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by reticulate pigmentation of the flexures. By direct DNA sequencing, we have identified a frameshift mutation in exon 1 of KRT5 in the proband from an extended Spanish DDD kindred. Cloning of PCR products confirmed that this was a 2-bp deletion mutation, designated c.442delAG, leading to a premature termination codon in the V1 domain of the K5 polypeptide, designated p.S148fsX30. These data confirm that haploinsufficiency for K5 causes DDD and points to a prominent role for the keratin intermediate filament cytoskeleton within basal keratinocytes in epidermal pigment biology.
authors.affiliation: Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Haihui
authors.initials: H
authors.lastname: Liao
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: David U
authors.initials: DU
authors.lastname: Baty
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.forename: Jemima E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
mesh_terms: D000328:Adult; D018388:Codon, Terminator; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D017495:Hyperpigmentation / Q000235:genetics* / Q000473:pathology; D053555:Keratin-5 / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D018388:Codon, Terminator; D053555:Keratin-5