根据星期二发表于2007 年3月20 日The American Journal of Human Genetics电子版中的文章,研究人员辨认出一个新的基因突变,会导致与X染色体有关的智力缺陷,目前还没有分子技术可诊断这种智力缺陷。
英国剑桥大学医学院的研究人员F. Lucy Raymond 及英国Wellcome Trust Sanger研究机构的Patrick S. Tarpey,在这篇文章中描述他们在发育严重迟缓的儿童身上,发现ZDHHC9基因完全失去功能。
ZDHHC9 是一个新发现的基因。之前研究人员还未预测到这个基因与智力缺陷有关。ZDHHC9之所以被发现,只是因为研究人员系统性地观察X 染色体上的所有基因。
研究人员透过这项大型的国际合作,从至少有二个男孩发生智力缺陷的250 个家庭中收集基因样品,以辨认导致X染色体相关之智力缺陷的新基因。与X染色体有关的智力缺陷是相当严重的。某些患者需要全天候照顾,而且无语言能力。这种疾病通常只发生于男性,目前为止只有一些相关基因被辨认出。
(资料来源 : Bio.com)
部分英文原文:
Am. J. Hum. Genet., 80:000, 2007
0002-9297/2007/8005-00XX$15.00
© 2007 by The American Society of Human Genetics. All rights reserved.
Report
Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus
F. Lucy Raymond,* Patrick S. Tarpey,* Sarah Edkins, Calli Tofts, Sarah O'Meara, Jon Teague, Adam Butler, Claire Stevens, Syd Barthorpe, Gemma Buck, Jennifer Cole, Ed Dicks, Kristian Gray, Kelly Halliday, Katy Hills, Jonathon Hinton, David Jones, Andrew Menzies, Janet Perry, Keiran Raine, Rebecca Shepherd, Alexandra Small, Jennifer Varian, Sara Widaa, Uma Mallya, Jenny Moon, Ying Luo, Marie Shaw, Jackie Boyle, Bronwyn Kerr, Gillian Turner, Oliver Quarrell, Trevor Cole, Douglas F. Easton, Richard Wooster, Martin Bobrow, Charles E. Schwartz, Jozef Gecz, Michael R. Stratton, and P. Andrew Futreal
From the Cambridge Institute of Medical Research, University of Cambridge (F.L.R.; U.M.; J.M.; Y.L.; M.B.), and Genetic Epidemiology Unit, Cancer Research UK (D.F.E.), Cambridge, United Kingdom; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom (P.S.T.; S.E.; C.T.; S.O.; J.T.; A.B.; C.S.; S.B.; G.B.; J.C.; E.D.; K.G.; K. Halliday; K. Hills; J.H.; D.J.; A.M.; J.P.; K.R.; R.S.; A.S.; J.V.; S.W.; M.S.; R.W.; M.R.S.; P.A.F.); Regional Genetics Service, St Mary's Hospital, Manchester, United Kingdom (B.K.); Genetics of Learning Disability (GOLD) Service, University of Newcastle, Newcastle, Australia (J.B.; G.T.); Clinical Genetics, Sheffield Children's Hospital, Sheffield, United Kingdom (O.Q.); Clinical Genetics, Birmingham Women's Hospital, Birmingham, United Kingdom (T.C.); JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC (C.E.S.); and Department of Genetic Medicine, Women's and Children's Hospital, and Departments of Paediatrics and Molecular Biosciences, University of Adelaide (M.S.; J.G.), Adelaide, Australia
Received January 11, 2007; accepted for publication February 7, 2007; electronically published March 20, 2007.
We have identified one frameshift mutation, one splice-site mutation, and two missense mutations in highly conserved residues in ZDHHC9 at Xq26.1 in 4 of 250 families with X-linked mental retardation (XLMR). In three of the families, the mental retardation phenotype is associated with a Marfanoid habitus, although none of the affected individuals meets the Ghent criteria for Marfan syndrome. ZDHHC9 is a palmitoyltransferase that catalyzes the posttranslational modification of NRAS and HRAS. The degree of palmitoylation determines the temporal and spatial location of these proteins in the plasma membrane and Golgi complex. The finding of mutations in ZDHHC9 suggests that alterations in the concentrations and cellular distribution of target proteins are sufficient to cause disease. This is the first XLMR gene to be reported that encodes a posttranslational modification enzyme, palmitoyltransferase. Furthermore, now that the first palmitoyltransferase that causes mental retardation has been identified, defects in other palmitoylation transferases become good candidates for causing other mental retardation syndromes.