Kondo Ikuko, Yamagata Hidehisa
Department of Hygiene, Ehime University School of Medicine, Onsengun, Ehime.
No To Hattatsu. 2002 May;34(3):219-23.
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder characterized by regression in cognition and adaptability with autistic behavior, stereotypical hand movements, epilepsy and ataxia. Over 120 different mutations in the methyl-CpG binding protein 2 gene (MECP2) have been reported in patients with RTT, but a genotype-phenotype correlation has not been established. We have studied MECP2 mutations in 142 Japanese sporadic patients diagnosed clinically as having RTT. Forty different mutations in MECP2 have been detected in 103 female patients. Common mutations were four missense mutations (T158M,P152R, R133C and R306C) observed in 34 cases and four nonsense mutations (R168X, R255X, R270X and R294X) detected in 38 cases. Among these, R133C, R306C, and R294X were associated with atypical RTT including the preserved speech variant type, T158M and R168X with typical clinical features of RTT, and P152R, R255X, and R270X with severe developmental delay. These results suggest a genotype-phenotype correlation RTT. However, a large scale study of adult RTT patients is required to determine more precisely the influence of MECP2 mutation types on the natural history and clinical phenotypes of RTT.
雷特综合征（RTT）是一种X连锁显性神经发育障碍，其特征为认知和适应性倒退，并伴有自闭症行为、刻板手部动作、癫痫和共济失调。在雷特综合征患者中已报道了甲基CpG结合蛋白2基因（MECP2）超过120种不同的突变，但尚未建立基因型与表型的相关性。我们研究了142例临床诊断为雷特综合征的日本散发性患者的MECP2突变。在103例女性患者中检测到MECP2的40种不同突变。常见突变包括在34例中观察到的4种错义突变（T158M、P152R、R133C和R306C）以及在38例中检测到的4种无义突变（R168X、R255X、R270X和R294X）。其中，R133C、R306C和R294X与非典型雷特综合征相关，包括保留言语变异型；T158M和R168X具有雷特综合征的典型临床特征；P152R、R255X和R270X与严重发育迟缓相关。这些结果提示雷特综合征存在基因型与表型的相关性。然而，需要对成年雷特综合征患者进行大规模研究，以更精确地确定MECP2突变类型对雷特综合征自然病史和临床表型的影响。
