Kleefstra Tjitske, Yntema Helger G, Nillesen Willy M, Oudakker Astrid R, Mullaart Reinier A, Geerdink Niels, van Bokhoven Hans, de Vries Bert B A, Sistermans Erik A, Hamel Ben C J
Department of Human Genetics, University Medical Centre St Radboud, PO Box 9101, Nijmegen 6500 HB, The Netherlands.
Eur J Hum Genet. 2004 Jan;12(1):24-8. doi: 10.1038/sj.ejhg.5201080.
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.
雷特综合征（RTT）是女性中最常见的神经发育障碍之一。该疾病由甲基CpG结合蛋白2基因（MECP2）突变引起，已报道了多种突变。女性和男性患者的表型谱各不相同，从非常轻微到先天性脑病和产前致死。在本研究中，探讨了在DNA诊断中对不明原因智力低下患者进行MECP2系统筛查是否合理，并进一步探索了该基因突变导致的表型谱。对FMR1 CGG重复扩增阴性的智障女性患者、临床特征提示安吉尔曼综合征或普拉德-威利综合征但15号染色体q11-q13无甲基化缺陷的男性和女性患者进行了MECP2突变分析。在分子脆性X研究阴性的女性队列（N=92）中，发现了一个无义突变（p.Q406X）。在安吉尔曼综合征阴性患者队列（N=63）中，发现了两个错义突变（一名女性患者为p.R133C，一名男性患者为嵌合型p.T158M），这些突变在经典RTT综合征患者中已多次报道。在普拉德-威利综合征阴性组（N=98）中，未发现致病突变。结果支持对临床特征提示安吉尔曼综合征但15号染色体q11-q13无甲基化缺陷的患者进行MECP2突变检测。对于其余不明原因智力低下的患者，应根据其他临床特征来决定是否进行MECP2分析。
