Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome -: art. no. e12
Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome -: art. no. e12
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DOI：
10.1136/jmg.2004.023804
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发表时间：
2005-02-01
影响因子：
4
通讯作者：
Epplen, JT
中科院分区：
文献类型：
--
作者：
Meins, M;Lehmann, J;Epplen, JT
Rett综合征是一种几乎只影响女孩的X连锁精神发育迟滞综合征，长期以来一直被认为是一种在半合子男性中致命的X连锁显性疾病。1编码甲基CpG结合蛋白2（MECP 2）的基因突变被证明是Rett综合征的原因，2并被许多研究证实。绝大多数（95%）的MECP 2突变发生从头。受“经典”Rett综合征影响的女孩表现出智力迟钝和退化，典型的症状模式包括最初正常发育，停滞，后天能力丧失，刻板的手部运动，言语退化，严重的精神发育迟滞，癫痫和自闭症，尽管分子诊断已经证明存在不同的临床形式。3 4最近的研究表明，MECP 2的错义突变可导致男孩严重的新生儿脑病。5到目前为止，男孩的经典Rett表型仅在体细胞嵌合体或XXY核型的罕见病例中报道。6-11在女孩中，较大的基因内缺失导致约11-16%的典型Rett综合征，编码外显子中没有点突变。12 13在男孩中尚未发现较大的缺失，MECP 2的重复尚未被报道为典型Rett综合征的原因。我们已经建立了定量PCR的缺失影响MECP 2的诊断，在本文中，我们报告了一个男孩表现出Rett综合征的临床特征和亚显微镜下重复内的细胞遗传学带Xq 28涵盖整个MECP 2基因。
Rett syndrome is an X linked mental retardation syndrome almost exclusively affecting girls, and has long been regarded as an X linked dominant condition lethal in hemizygous males. 1 Mutations in the gene encoding the methyl-CpG binding protein 2 (MECP2) were demonstrated as the cause of Rett syndrome, 2 and confirmed by a number of studies. The vast majority (95%) of MECP2 mutations occurs de novo. Girls affected by ‘‘classic’’Rett syndrome show mental retardation and regression, with a typical pattern of symptoms including initially normal development, stagnation, loss of acquired abilities, stereotypic hand movements, regression of speech, profound psychomotor retardation, epilepsy, and autism, although molecular diagnostics has proven that variant clinical forms exist. 3 4It has recently been shown that missense mutations in MECP2 can cause severe neonatal encephalopathy in boys. 5 Classic Rett phenotypes in boys have so far only been reported in rare cases of somatic mosaicism or XXY karyotypes. 6–11 In girls, larger intragenic deletions are responsible for about 11–16% of typical Rett syndrome without point mutations in the coding exons. 12 13 Larger deletions have not yet been found in boys, and duplications of MECP2 have not yet been reported as a cause for typical Rett syndrome at all. We have established quantitative PCR for diagnosis of deletions affecting MECP2, and in this paper, we report a boy manifesting clinical features of Rett syndrome and a submicroscopic duplication within the cytogenetic band Xq28 encompassing the entire MECP2 gene.