title: A missense mutation within the helix initiation motif of the keratin K71 gene underlies autosomal dominant woolly hair/hypotrichosis.
abstract: Woolly hair (WH) is an abnormal variant of tightly curled hair, which is frequently associated with hypotrichosis. Non-syndromic forms of WH can show either autosomal-dominant WH (ADWH) or autosomal-recessive WH (ARWH) inheritance patterns. ARWH has recently been shown to be caused by mutations in either the lysophosphatidic acid receptor 6 (LPAR6) or lipase H (LIPH) gene. More recently, a mutation in the keratin K74 (KRT74) gene has been reported to underlie ADWH. Importantly, all of these genes are abundantly expressed in the inner root sheath (IRS) of human hair follicles. Besides these findings, the molecular mechanisms underlying hereditary WH have not been fully disclosed. In this study, we identified a Japanese family with ADWH and associated hypotrichosis. After exclusion of known causative genes, we discovered the heterozygous mutation c.422T>G (p.Phe141Cys) within the helix initiation motif of the IRS-specific keratin K71 (KRT71) gene in affected family members. We demonstrated that the mutant K71 protein led to disruption of keratin intermediate filament formation in cultured cells. To our knowledge, it is previously unreported that the KRT71 mutation is associated with a hereditary hair disorder in humans. Our findings further underscore the crucial role of the IRS-specific keratins in hair follicle development and hair growth in humans.
authors.affiliation: Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujimoto
authors.affiliation: Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Farooq
authors.affiliation: Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujikawa
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohyama
authors.affiliation: Shiseido Research Center, Shin-Yokohama, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ehama
authors.affiliation: Shiseido Research Center, Shin-Yokohama, Japan.
authors.forename: Jotaro
authors.initials: J
authors.lastname: Nakanishi
authors.affiliation: Shiseido Research Center, Shin-Yokohama, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Hagihara
authors.affiliation: Shiseido Research Center, Shin-Yokohama, Japan.
authors.forename: Tokuro
authors.initials: T
authors.lastname: Iwabuchi
authors.affiliation: Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: yshimo@med.niigata-u.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics*; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006197:Hair / Q000254:growth & development; D006201:Hair Diseases / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development; D006579:Heterozygote; D006801:Humans; D007039:Hypotrichosis / Q000453:epidemiology* / Q000235:genetics*; D053564:Keratins, Hair-Specific / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree
chemical_list: C456200:KRT71 protein, human; D053564:Keratins, Hair-Specific