pubmed.ncbi.nlm.nih.gov

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

Case Reports

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

Yaran Wen et al. Nat Genet. 2009 Feb.

Erratum in

  • Nat Genet. 2009 Jun;41(6):762

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.

PubMed Disclaimer

Comment in

  • Hair lost in translation.

    Weiner L, Brissette JL. Weiner L, et al. Nat Genet. 2009 Feb;41(2):141-2. doi: 10.1038/ng0209-141. Nat Genet. 2009. PMID: 19174834 No abstract available.

Similar articles

Cited by

References

    1. Nat Rev Genet. 2007 Sep;8(9):711-23 - PubMed
    1. Hum Mol Genet. 1998 Oct;7(11):1671-9 - PubMed
    1. Am J Hum Genet. 1999 Aug;65(2):413-9 - PubMed
    1. Nat Genet. 1998 Jan;18(1):49-52 - PubMed
    1. J Invest Dermatol. 2005 Oct;125(4):711-4 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources