Reiss A L, Abrams M T, Greenlaw R, Freund L, Denckla M B
Kennedy Krieger Institute, Baltimore, Maryland 21205, USA.
Nat Med. 1995 Feb;1(2):159-67. doi: 10.1038/nm0295-159.
Brain dysfunction is the most important sequelae of the fragile X (FMR-1) mutation, the most common heritable cause of developmental disability. Using magnetic resonance imaging (MRI) and quantitative morphometry, we have compared the neuroanatomy of 51 individuals with an FMR-1 mutation with matched controls and showed that subjects with an FMR-1 mutation have increased volume of the caudate nucleus and, in males, the lateral ventricle. Both caudate and lateral ventricular volumes are correlated with IQ. Caudate volume is also correlated with the methylation status of the FMR-1 gene. Neuroanatomical differences between two monozygotic twins with an FMR-1 mutation who are discordant for mental retardation are localized to the cerebellum, lateral ventricles and subcortical nuclei. These findings suggest that the FMR-1 mutation causing the fragile X syndrome leads to observable changes in neuroanatomy that may be relevant to the neurodevelopmental disability and behavioural problems observed in affected individuals.
脑功能障碍是脆性X（FMR - 1）突变最重要的后遗症，而脆性X突变是发育障碍最常见的遗传病因。我们使用磁共振成像（MRI）和定量形态测量法，将51名FMR - 1突变个体的神经解剖结构与匹配的对照组进行了比较，结果显示，FMR - 1突变个体的尾状核体积增大，男性的侧脑室体积也增大。尾状核和侧脑室的体积均与智商相关。尾状核体积还与FMR - 1基因的甲基化状态相关。一对患有FMR - 1突变的同卵双胞胎，其中智力发育迟缓不一致的两人之间的神经解剖差异定位于小脑、侧脑室和皮质下核。这些发现表明，导致脆性X综合征的FMR - 1突变会引起神经解剖结构的可观察到的变化，这可能与受影响个体中观察到的神经发育障碍和行为问题有关。
