Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.

Wen, Y., Liu, Y., Xu, Y., Zhao, Y., Hua, R., Wang, K., et al. (2009). Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. NATURE GENETICS, 41(2), 228-233 [10.1038/ng.276].

Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis

Xu Y.;Terrinoni A.;Jiang L.;Zhang X.
2009

Abstract

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/12
English
Con Impact Factor ISI
Adolescent; Amino Acid Sequence; Base Sequence; Child; China; Down-Regulation; Family; Female; Humans; Hypotrichosis; Male; Middle Aged; Molecular Sequence Data; Open Reading Frames; Pedigree; Protein Biosynthesis; Regulatory Sequences, Nucleic Acid; Sequence Homology, Nucleic Acid; Transcription Factors; Mutation, Missense
Wen, Y., Liu, Y., Xu, Y., Zhao, Y., Hua, R., Wang, K., et al. (2009). Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. NATURE GENETICS, 41(2), 228-233 [10.1038/ng.276].
Wen, Y; Liu, Y; Xu, Y; Zhao, Y; Hua, R; Wang, K; Sun, M; Li, Y; Yang, S; Zhang, X-; Kruse, R; Cichon, S; Betz, Rc; Nothen, Mm; Van Steensel, Mam; Van Geel, M; Steijlen, Pm; Hohl, D; Huber, M; Dunnill, Gs; Kennedy, C; Messenger, A; Munro, Cs; Terrinoni, A; Hovnanian, A; Bodemer, C; De Prost, Y; Paller, As; Irvine, Ad; Sinclair, R; Green, J; Shang, D; Liu, Q; Luo, Y; Jiang, L; Chen, H-; Lo, WH-; Mclean, Whi; He, C-; Zhang, X
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/240696
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