Luo Shiyu, Huang Wen, Xia Qiuping, Du Qian, Wu Lingqian, Duan Ranhui
State Key Laboratory of Medical Genetics, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
State Key Laboratory of Medical Genetics, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China
J Child Neurol. 2015 May;30(6):803-6. doi: 10.1177/0883073814538508. Epub 2014 Jun 23.
CGG repeat expansion is the most common cause of fragile X syndrome. Numerous efforts have been made to identify novel mutations in patients with intellectual disability, developmental delay, and/or autism. To evaluate the mutational spectrum in the at-risk Chinese population, 60 pediatric patients presenting fragile X traits but normal-sized CGG repeats were sequenced for all 17 exons and regulatory regions in FMR1. A c.879A>C mutation, reported to alter a neighboring splicing, was detected in a severely retarded male and his normal mother. However, the exon junction appears unaffected. A 237-kb deletion covering the entire FMR1 was identified to cause moderate intellectual disability and marked hyperactivity in an 8-year-old boy. The 5' and 3' breakpoints were buried in the surrounding long interspersed and short interspersed elements, respectively. In general, missense mutations do not commonly cause fragile X syndrome, whereas deletions should be considered with caution in patient referrals presenting with developmental delay and/or ordinary retardation.
CGG重复序列扩增是脆性X综合征最常见的病因。人们已付出诸多努力来鉴定智力残疾、发育迟缓及/或自闭症患者中的新型突变。为评估高危中国人群中的突变谱，对60名表现出脆性X特征但CGG重复序列长度正常的儿科患者的FMR1基因全部17个外显子及调控区域进行了测序。在一名重度智力发育迟缓男性及其正常母亲中检测到一个c.879A>C突变，据报道该突变会改变相邻剪接。然而，外显子连接似乎未受影响。在一名8岁男孩中发现一个覆盖整个FMR1基因的237kb缺失，导致其中度智力残疾及明显多动。5′和3′断点分别位于周围的长散在元件和短散在元件中。一般而言，错义突变通常不会导致脆性X综合征，而对于有发育迟缓及/或普通智力迟钝表现的患者转诊时，应谨慎考虑缺失情况。
