title: A novel substitution in keratin 10 in epidermolytic hyperkeratosis.
abstract: Epidermolytic hyperkeratosis is characterized by tonofilament clumping, cytolysis, and blister formation in suprabasal keratinocytes. It has been shown that the tonofilament aggregates in these areas are composed of keratin 1 (K1) and keratin 10 (K10), and several K1 and K10 point mutations have been identified as the molecular basis of epidermolytic hyperkeratosis. In this report we identify a novel, single base pair substitution resulting in an amino acid exchange from tyrosine to serine at residue 14 within the conserved 1A region of K10 (Y14S). This A to C transversion in codon 160 was only present in the affected individual and was associated with a very severe disease phenotype. Our observations are in agreement with previous reports documenting that this tyrosine residue, located at the beginning of the rod domain of type I keratins, is particularly sensitive to amino acid substitutions, and that alterations in this residue can have deleterious effects on filament assembly and stability.
authors: Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: M J
authors: MJ
authors: Arin
authors: M A
authors: MA
authors: Longley
authors: I
authors: I
authors: Anton-Lamprecht
authors: G
authors: G
authors: Kurze
authors: M
authors: M
authors: Huber
authors: D
authors: D
authors: Hohl
authors: J A
authors: JA
authors: Rothnagel
authors: D R
authors: DR
authors: Roop
mesh_terms: D002675:Child, Preschool; D005260:Female; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics* / Q000473:pathology; D053550:Keratin-10; D007633:Keratins / Q000737:chemistry / Q000235:genetics*; D008297:Male; D017354:Point Mutation
chemical_list: C507493:KRT10 protein, human; D053550:Keratin-10; D007633:Keratins