MECP2 analysis in mentally retarded patients:: implications for routine DNA diagnostics
MECP2 analysis in mentally retarded patients:: implications for routine DNA diagnostics
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DOI：
10.1038/sj.ejhg.5201080
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发表时间：
2004-01-01
影响因子：
5.2
通讯作者：
Hamel, BCJ
中科院分区：
文献类型：
--
作者：
Kleefstra, T;Yntema, HG;Hamel, BCJ
Rett综合征(RTT)是女性最常见的神经发育障碍之一。这种疾病是由甲基CpG结合蛋白2基因(MECP2)突变引起的，已有各种突变的报道。女性和男性患者的表型谱都是不同的，从非常轻微的到先天性脑病和产前死亡。本研究探讨了在DNA诊断中对不明原因智力低下患者实施MECP2基因系统筛查是否合理，并进一步探讨了该基因突变导致的表型谱。对FMR1 CGG重复扩增阴性的精神发育迟滞女性患者进行MECP2突变分析，对临床特征提示Angelman或Prader-Willi综合征且无染色体15q11-q13甲基化缺陷的男性和女性患者进行检测。在分子脆性X研究阴性的女性队列中(N=92)，发现一个无义突变(p.Q406X)。在Angelman阴性患者队列中(N=63)，发现两个错义突变(女性患者中的p.R133C和男性患者中的嵌合体p.T158M)，这在经典型RTT综合征患者中已被多次报道。在Prader-Willi阴性组(N=98)中，没有发现致病突变。结果支持对具有Angelman综合征特征但在染色体15q11-q13上没有甲基化缺陷的患者进行MECP2突变检测。在其余原因不明的智力低下患者中，其他临床特征应决定是否有MECP2分析的指征。
Rett syndrome (RTT) is one of the most common neurodevelopmental disorders in females. The disease is caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2), and various mutations have been reported. The phenotypic spectrum in both female and male patients is diverse, ranging from very mild to congenital encephalopathy and prenatal lethality. In this study, the question was addressed as to whether implementation of systematic screening of MECP2 in patients with an unexplained mental retardation in DNA diagnostics would be reasonable, and the spectrum of phenotypes resulting from mutations in this gene was further explored. Mutational analysis of MECP2 was performed in mentally retarded female patients who were negative for FMR1 CGG repeat expansion, in male and female patients with clinical features suggestive of either Angelman or Prader-Willi syndrome without methylation defects on chromosome 15q11-q13. In the cohort of females negative for the molecular Fragile-X studies (N = 92), one nonsense mutation (p.Q406X) was found. In the cohort of Angelman-negative patients (N = 63), two missense mutations (p.R133C in a female patient and a mosaic p.T158M in a male patient) were found, which have been reported many times in patients with classical RTT syndrome. In the Prader-Willi-negative group (N = 98), no pathogenic mutations were found.The results support testing of patients with features suggestive of Angelman syndrome, but without methylation defects on chromosome 15q11-q13 for mutations in MECP2. In the remaining patients with unexplained mental retardation, additional clinical features should determine whether analysis of MECP2 is indicated.