Yamada Y, Miura K, Kumagai T, Hayakawa C, Miyazaki S, Matsumoto A, Kurosawa K, Nomura N, Taniguchi H, Sonta S I, Yamanaka T, Wakamatsu N
Department of Genetics, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan.
Hum Mutat. 2001 Sep;18(3):253. doi: 10.1002/humu.1186.
Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects females almost exclusively. The recent identification of mutations of the methyl-CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze the gene in 37 Japanese patients divided into classical RTT (14 cases), variant RTT (13 cases), and mentally retarded patients with Rett-like features (10 cases). Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). Six reported common mutations were detected in 17 cases, and rare single nucleotide substitutions were found in 3 patients. In addition, one insertion mutation (1189insA) and four deletion mutations including one double deletion mutant (451delG, 100del4, 1124del53 and 881del289 plus 1187del8) were newly identified. In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT indicates that RTT fulfilling the diagnostic criteria are due to genetic alteration.
瑞特综合征是一种几乎仅影响女性的X连锁显性神经发育障碍疾病。最近在瑞特综合征患者中发现甲基化CpG结合蛋白2基因（MECP2）的突变，促使我们对37名日本患者的该基因进行分析，这些患者分为典型瑞特综合征（14例）、变异型瑞特综合征（13例）以及具有瑞特样特征的智力发育迟缓患者（10例）。在大多数典型和变异型瑞特综合征患者（27例中的25例）中发现了MECP2突变。在17例患者中检测到6种已报道的常见突变，3例患者中发现了罕见的单核苷酸替代。此外，新发现了1种插入突变（1189insA）和4种缺失突变，其中包括1种双缺失突变体（451delG、100del4、1124del53和881del289加1187del8）。然而，在10例具有瑞特样特征的智力发育迟缓患者中，未在MECP2编码区检测到突变。92.5%的瑞特综合征患者中发现MECP2突变，这一发现表明符合诊断标准的瑞特综合征是由基因改变引起的。
