2. Academic Validation
  3. Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis

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

  • Nat Genet. 2009 Feb;41(2):228-33. doi: 10.1038/ng.276.
Yaran Wen 1,  Yang Liu,  Yiming Xu,  Yiwei Zhao,  Rui Hua,  Kaibo Wang,  Miao Sun,  Yuanhong Li,  Sen Yang,  Xue-Jun Zhang,  Roland Kruse,  Sven Cichon,  Regina C Betz,  Markus M Nöthen,  Maurice A M van Steensel,  Michel van Geel,  Peter M Steijlen,  Daniel Hohl,  Marcel Huber,  Giles S Dunnill,  Cameron Kennedy,  Andrew Messenger,  Colin S Munro,  Alessandro Terrinoni,  Alain Hovnanian,  Christine Bodemer,  Yves de Prost,  Amy S Paller,  Alan D Irvine,  Rod Sinclair,  Jack Green,  Dandan Shang,  Qing Liu,  Yang Luo,  Li Jiang,  Hong-Duo Chen,  Wilson H-Y Lo,  W H Irwin McLean,  Chun-Di He,  Xue Zhang
Affiliations

Affiliation

  • 1 McKusick-Zhang Center for Genetic Medicine and National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
PMID: 19122663 DOI: 10.1038/ng.276
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.

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