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

Yaran Wen, 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. DunnillCameron 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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)228-233
Number of pages6
JournalNature Genetics
Issue number2
Publication statusPublished - Feb 2009

ASJC Scopus subject areas

  • Genetics


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