A missense mutation within the helix initiation motif of the keratin K71 gene underlies autosomal dominant woolly hair/hypotrichosis

Atsushi Fujimoto, Muhammad Farooq, Hiroki Fujikawa, Asuka Inoue, Manabu Ohyama, Ritsuko Ehama, Jotaro Nakanishi, Motofumi Hagihara, Tokuro Iwabuchi, Junken Aoki, Masaaki Ito, Yutaka Shimomura

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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.422TG (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.

Original languageEnglish
Pages (from-to)2342-2349
Number of pages8
JournalJournal of Investigative Dermatology
Issue number10
Publication statusPublished - 2012 Oct


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Fujimoto, A., Farooq, M., Fujikawa, H., Inoue, A., Ohyama, M., Ehama, R., Nakanishi, J., Hagihara, M., Iwabuchi, T., Aoki, J., Ito, M., & Shimomura, Y. (2012). A missense mutation within the helix initiation motif of the keratin K71 gene underlies autosomal dominant woolly hair/hypotrichosis. Journal of Investigative Dermatology, 132(10), 2342-2349. https://doi.org/10.1038/jid.2012.154