1月4日,，《自然—遺傳學(xué)》（Nature Genetics）在線發(fā)表由中國醫(yī)學(xué)科學(xué)院張學(xué)教授領(lǐng)導(dǎo)的研究團隊的發(fā)現(xiàn)表明，一種以前未知的由HR基因引導(dǎo)序列編碼的小肽,，其突變可降低小肽的功能進而引起一種罕見的遺傳性脫發(fā),。作者認為，這一小肽為研發(fā)治療人類某些類型脫發(fā)的藥物提供了一個新的靶點,。
國外研究者在十年前已證明HR基因突變是導(dǎo)致先天性無毛癥（一種罕見的脫發(fā)形式）的原因,。先天性無毛癥的患兒，一歲之內(nèi)毛發(fā)就完全脫落且不會再生,。Marie Unna遺傳性稀毛癥,，簡稱為MUHH，是一種與先天性無毛癥有關(guān)但病程不同的脫發(fā)形式,。先天性無毛癥呈常染色體隱性遺傳而MUHH則表現(xiàn)為常染色體顯性遺傳,。MUHH已經(jīng)被定位到含有HR基因的一個較小的染色體區(qū)域，但還一直沒在MUHH患者中發(fā)現(xiàn)該基因的突變。
張學(xué)教授領(lǐng)導(dǎo)的國際聯(lián)合研究團隊發(fā)現(xiàn),，直接比鄰HR基因編碼區(qū)的引導(dǎo)序列（又稱5’非翻譯區(qū),，即5’UTR）編碼一種由34個氨基酸組成的小肽（命名為U2HR），在來自不同國家的19個MUHH家系中存在影響U2HR功能的突變,。有趣的是,，張學(xué)教授實驗室的研究結(jié)果提示，U2HR的功能是抑制HR基因自身的蛋白質(zhì)合成過程,，U2HR的致病突變卻是引起HR蛋白量的增加,。因此，HR蛋白水平必須維持在一定范圍內(nèi)才能阻止毛發(fā)脫落,。
在U2HR發(fā)現(xiàn)MUHH致病突變的意義不僅僅在于揭示遺傳性脫發(fā)的一種新機制,，同時也證明基因非翻譯區(qū)同樣也可以是致病突變發(fā)生的主要部位。
研究小組包括中國醫(yī)學(xué)科學(xué)院-北京協(xié)和醫(yī)學(xué)院和中國醫(yī)科大學(xué)的研究人員及皮膚科醫(yī)生組成的研究團隊,，聯(lián)合包括中國,、英國、德國,、荷蘭,、法國、瑞士,、意大利,、美國、愛爾蘭和澳大利亞共十個國家的相關(guān)課題組,，在張學(xué)教授,、何春滌教授和英國Irwin McLean教授的領(lǐng)導(dǎo)和協(xié)調(diào)下完成。研究經(jīng)費資助的主要來源為國家自然科學(xué)基金重點項目和創(chuàng)新群體項目,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Genetics,，doi:10.1038/ng.276，Chun-Di He,，Xue Zhang
Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis
Yaran Wen1,21, Yang Liu2,21, Yiming Xu1,21, Yiwei Zhao3,21, Rui Hua1, Kaibo Wang4, Miao Sun1, Yuanhong Li4, Sen Yang5, Xue-Jun Zhang5, Roland Kruse6, Sven Cichon7,8, Regina C Betz7, Markus M N?then7,8, Maurice A M van Steensel9, Michel van Geel9, Peter M Steijlen9, Daniel Hohl10, Marcel Huber10, Giles S Dunnill11, Cameron Kennedy11, Andrew Messenger12, Colin S Munro13, Alessandro Terrinoni14, Alain Hovnanian15, Christine Bodemer16, Yves de Prost16, Amy S Paller17, Alan D Irvine18,19, Rod Sinclair20, Jack Green20, Dandan Shang1, Qing Liu1, Yang Luo2, Li Jiang2, Hong-Duo Chen4, Wilson H-Y Lo1, W H Irwin McLean3, Chun-Di He4 & Xue Zhang1,2
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.
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.
2 The Research Center for Medical Genomics, China Medical University, Shenyang 110001, China.
3 Epithelial Genetics Group, Division of Molecular Medicine, Colleges of Life Sciences and Medicine, Dentistry & Nursing, University of Dundee, Dundee DD1 5EH, Scotland, UK.
4 Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang 110001, China.
5 Institute of Dermatology, Anhui Medical University, Hefei 230032, China.
6 Department of Dermatology, University of Düsseldorf, D-40225 Düsseldorf, Germany.
7 Institute of Human Genetics, University of Bonn, D-53111 Bonn, Germany.
8 Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany.
9 Maastricht University Center for Molecular Dermatology, University Hospital Maastricht, 6202AZ Maastricht, The Netherlands.
10 CHUV, H?pital de Beaumont, CH-1011 Lausanne, Switzerland.
11 Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
12 Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
13 Department of Dermatology, Southern General Hospital, Glasgow G51 4TF, UK.
14 IDI-IRCCS Biochemistry Laboratory, University of Tor Vergata, 00133 Rome, Italy.
15 INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse F-313000, France.
16 Department of Dermatology, Necker Hospital, 75105 Paris, France.
17 Departments of Dermatology and Pediatrics, Northwestern University, Chicago, Illinois 60611, USA.
18 Department of Paediatric Dermatology, Our Lady's Children's Hospital, Dublin 12, Ireland.
19 Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland.
20 Department of Dermatology, St. Vincent's Hospital, Melbourne, Victoria 3065, Australia.
21 These authors contributed equally to this work.
