TARGETED INVESTIGATION OF DISTAL XQ IN RETT SYNDROME

描述：（改编自研究者摘要）Rett综合征是一种 神经发育障碍影响全世界1/10，000 - 15，000的女性。 出生时看起来正常，患有Rett综合征的女孩 回归并获得神经和行为特征， 来定义这种疾病的诊断标准虽然Rett综合征 一般发生零星罕见的家族复发表明遗传 紊乱的基础。有几个特征与X连锁的 显性位点包括：（1）经典表型的排他性发生 女性;（2）Rett综合征中严重受累男性的识别 遗传学;（3）母亲传给女儿;（4）非随机X染色体 非显性专性携带者女性的失活模式。 来自这些复发性Rett综合征罕见家族的排除作图数据 将该基因定位于X染色体的远端长臂（Xq27.3-Xqter）。的 该建议的重点是使用 结合分子和细胞遗传学方法。根据他们以前的工作， 加州大学洛杉矶分校新人类遗传学系的环境和资源，他们是 非常适合进行这些研究。调查将检验 三个主要假设使用组合的分子和细胞遗传学方法。

DESCRIPTION: (Adapted from investigator's abstract) Rett syndrome is a neurodevelopmental disorder affecting 1 in 10,000-15,000 females worldwide. Apparently normal at birth, girls with Rett syndrome undergo developmental regression and acquire a neurologic and behavioral profile which has been used to define diagnostic criteria for the disorder. Although Rett syndrome generally occurs sporadically rare familial recurrences indicate a genetic basis for the disorder. Several features are consistent with an X-linked dominant locus including: (1) the exclusive occurrence of the classic phenotype in females; (2) the identification of severely affected males in Rett syndrome kindreds; (3) mother to daughter transmission; and (4) non-random X-chromosome inactivation patterns in nonmanifesting obligate carrier females. Exclusion mapping data from these rare families with recurrent Rett syndrome localize the gene to the distal long am of the X chromosome (Xq27.3-Xqter). The focus of this proposal is the identification of the causative gene using combined molecular and cytogenetic approaches. Based on their previous work and the milieu and resources of the new Human Genetics department at UCLA, they are in an excellent position to perform these studies. The investigations will test three primary hypotheses using combined molecular and cytogenetic approaches.