Zhu Xingwang, Li Meirong, Pan Hong, Bao Xinhua, Zhang Jingjing, Wu Xiru
Department of Pediatrics, Peking University First Hospital, Beijing, People's Republic of China.
J Child Neurol. 2010 Jul;25(7):842-8. doi: 10.1177/0883073809350722. Epub 2010 Mar 5.
Rett syndrome is an X-linked neurodevelopmental disorder that predominantly affects females. It is caused by mutations in methyl-CpG-binding protein 2 gene. Due to the sex-limited expression, it has been suggested that de novo X-linked mutations may exclusively occur in male germ cells and thus only females are affected. In this study, the authors have analyzed the parental origin of mutations and the X-chromosome inactivation status in 24 sporadic patients with identified methyl-CpG-binding protein 2 gene mutations. The results showed that 22 of 24 patients have a paternal origin. Only 2 patients have a maternal origin. Except for 2 cases which were homozygotic at the androgen receptor gene locus, of the remaining 22 cases, 16 cases have a random X-chromosome inactivation pattern; the other 6 cases have a skewed X-chromosome inactivation and they favor expression of the wild allele. The relationship between X-chromosome inactivation and phenotype may need more cases to explore.
雷特综合征是一种主要影响女性的X连锁神经发育障碍。它由甲基CpG结合蛋白2基因突变引起。由于其性别限制表达，有人提出新发X连锁突变可能仅发生在雄性生殖细胞中，因此只有女性会受到影响。在本研究中，作者分析了24例已鉴定出甲基CpG结合蛋白2基因突变的散发性患者的突变亲本来源和X染色体失活状态。结果显示，24例患者中有22例突变来自父亲。只有2例突变来自母亲。除了2例在雄激素受体基因位点为纯合子的病例外，其余22例中，16例具有随机的X染色体失活模式；另外6例具有偏态X染色体失活，且它们倾向于野生等位基因的表达。X染色体失活与表型之间的关系可能需要更多病例来探索。
