title: An alanine to proline mutation in the 1A rod domain of the keratin 10 chain in epidermolytic hyperkeratosis.
abstract: We report a mutation in a case of epidermolytic hyperkeratosis that results in a proline for alanine substitution in the residue position 12 of the 1A subdomain of the keratin 10 chain (codon 158). The disease phenotype is consistent with the inappropriate substitution of a proline near the beginning of the rod domain, because it is likely to seriously disrupt the structural organization of coiled-coil molecules within keratin intermediate filaments. Mutations/substitutions in this position have not been reported in any keratin disease. Position 12 is an alanine in all intermediate filament chains, and lies in the outer b heptad position of the coiled-coil. In vitro peptide interference assembly assays revealed that substitutions that alter residue size or charge at this position primarily interfere with keratin filament elongation.
authors.affiliation: Department of Dermatology, College of Medicine, Sung Kyun Kwan University, Seoul, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Yang
authors.forename: K
authors.initials: K
authors.lastname: Yoneda
authors.forename: E
authors.initials: E
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Imamura
authors.forename: K
authors.initials: K
authors.lastname: Nam
authors.forename: E S
authors.initials: ES
authors.lastname: Lee
authors.forename: P M
authors.initials: PM
authors.lastname: Steinert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000409:Alanine / Q000235:genetics*; D005260:Female; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics*; D007382:Intermediate Filaments / Q000737:chemistry; D007633:Keratins / Q000737:chemistry* / Q000235:genetics; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011392:Proline / Q000235:genetics*; D017434:Protein Structure, Tertiary
chemical_list: D007633:Keratins; D011392:Proline; D000409:Alanine