生物谷报道：MECP2的突变可以导致持续性神经系统退化性疾病---Rett综合征。这个x-染色体连锁综合征（X-linked syndrome）主要在女性身上体现，但相对温和的突变也可以导致男性的智力障碍(mental retardation)。
比利时勒芬市Gasthuisberg大学医院Hilde Van Esch和他同事最近报道在有智力障碍和神经系统退化的男性当中，发现了包括MECP2基因在内的重复的基因组序列。这种序列重复共在四个病患身上发现：三个患有x-染色体连锁的智力障碍，一个患有偶发性智力障碍。重复区域长度一般是450 kb，除了MECP2外，还有9个其他的基因存在其中。以前有研究提示MECP2的表达，不管过多还是过少，都对神经元的功能有害。所以，当发现含有多copy序列的人体身上MECP2的表达有所升高，作者认为MECP2可以对智力障碍这一表型起到决定性作用。
这一研究成果，使女性Rett综合征已经有了新的检测方法。同时，今后只要对MECP2拷贝数的定量分析，也会对男性中偶发性智力障碍的检测提供有效工具。
参看英文原文：
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综合征基因突变的已知表型数据库
http://homepages.ed.ac.uk/skirmis/
下面是介绍性文章，是有关MECP2基因与Rett综合征研究的进展。
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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