Vacca M, Filippini F, Budillon A, Rossi V, Mercadante G, Manzati E, Gualandi F, Bigoni S, Trabanelli C, Pini G, Calzolari E, Ferlini A, Meloni I, Hayek G, Zappella M, Renieri A, D'Urso M, D'Esposito M, MacDonald F, Kerr A, Dhanjal S, Hultén M
International Institute of Genetics and Biophysics, CNR, Naples, Italy.
J Mol Med (Berl). 2001;78(11):648-55. doi: 10.1007/s001090000155.
Rett syndrome is an X-linked dominant neurological disorder, which appears to be the commonest genetic cause of profound combined intellectual and physical disability in Caucasian females. Recently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed. We review the literature on MECP2 mutations in Rett syndrome. This analysis has permitted us to produce a map of the recurrent mutations identified in this and previous studies. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, which is conserved among brain-specific regulatory factors.
雷特综合征是一种X连锁显性神经障碍疾病，它似乎是白种女性中导致严重智力和身体残疾的最常见遗传病因。最近，该综合征与MECP2基因的突变有关，MECP2基因是一种转录抑制因子，其靶基因尚不清楚。在此，我们报告了对来自英国和意大利档案的62例患者的详细突变分析，这是首次在不同人群中进行的比较研究，也是迄今为止分析病例数最多的研究之一。我们回顾了关于雷特综合征中MECP2突变的文献。这项分析使我们能够绘制出在本研究和以往研究中确定的复发性突变图谱。利用结构和进化数据对这些突变进行生物信息学分析，使我们推测在MeCP2蛋白中存在一个新的功能域，该功能域在脑特异性调节因子中是保守的。
