生物谷報道：MECP2的突變可以導(dǎo)致持續(xù)性神經(jīng)系統(tǒng)退化性疾病---Rett綜合征,。這個x-染色體連鎖綜合征（X-linked syndrome）主要在女性身上體現(xiàn),，但相對溫和的突變也可以導(dǎo)致男性的智力障礙(mental retardation),。
比利時勒芬市Gasthuisberg大學(xué)醫(yī)院Hilde Van Esch和他同事最近報道在有智力障礙和神經(jīng)系統(tǒng)退化的男性當(dāng)中,，發(fā)現(xiàn)了包括MECP2基因在內(nèi)的重復(fù)的基因組序列,。這種序列重復(fù)共在四個病患身上發(fā)現(xiàn)：三個患有x-染色體連鎖的智力障礙,，一個患有偶發(fā)性智力障礙,。重復(fù)區(qū)域長度一般是450 kb,，除了MECP2外,，還有9個其他的基因存在其中。以前有研究提示MECP2的表達(dá),，不管過多還是過少,，都對神經(jīng)元的功能有害。所以,，當(dāng)發(fā)現(xiàn)含有多copy序列的人體身上MECP2的表達(dá)有所升高,，作者認(rèn)為MECP2可以對智力障礙這一表型起到?jīng)Q定性作用。
這一研究成果,，使女性Rett綜合征已經(jīng)有了新的檢測方法,。同時，今后只要對MECP2拷貝數(shù)的定量分析,，也會對男性中偶發(fā)性智力障礙的檢測提供有效工具,。
參看英文原文：
Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, Lugtenberg D, Bienvenu T, Jensen LR, Gecz J, Moraine C, Marynen P, Fryns JP, Froyen G. Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males. Am J Hum Genet. 2005 Sep;77(3):442-53.
Rett綜合征基因突變的已知表型數(shù)據(jù)庫
http://homepages.ed.ac.uk/skirmis/
下面是介紹性文章，是有關(guān)MECP2基因與Rett綜合征研究的進(jìn)展,。
We suspect that most of these mutations result in a non-functional protein. Many missense mutations which occur within the Methyl CpG binding domain (MBD) are known to interfere with the structure of the domain.
Methyl-CpG Binding Domain of MeCP2
(Andrew Free and Brian Smith, ICMB, University of Edinburgh)
Mutation Frequency in Rett Syndrome
X Marks the Spot
The MECP2 gene is located X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. Thus females consist of a mixture of cells in which either one or the other X chromosome is inactivated. In girls suffering from Rett Syndrome, one of their X chromosomes, usually that inherited from their father, contains a nonfunctional MeCP2 gene. Random X chromosome inactivation means that while half of their cells happen to have inactivated the mutant chromosome, half have inactivated the chromosome bearing the only functional copy of MeCP2 that they have. So they are effectively a mixture of cells containing 100% levels of MeCP2 activity and cells containing no functional MeCP2 at all.
Normal males only have one X chromosome, and only one copy of the MECP2 gene. If they inherited a mutated MECP2 gene, then every cell in their body will be devoid of MeCP2 activity. The fact that most MECP2 mutations arise in the paternal germ line means that males, who inherit their X chromosome from their mother (and a Y chromosome from their fathers) are less likely to inherit a MeCP2 mutation than are females.
We used to think that males inheriting a MeCP2 mutation died before birth, but we now know that this is probably not true. Several males have now been found who have inherited MeCP2 mutations which, when present in a girl, will give rise to Rett Syndrome. These unfortunate males appear normal at birth, but develp encephalopathy and breating abnormalities within a few days of being born. There is a general failure to thrive, and they die within two years of age. We are provisionally referring to these males as having Male Rett Mutation (MRM) syndrome.
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