TARGETED INVESTIGATION OF DISTAL XQ IN RETT SYNDROME

描述：(改编自研究人员摘要)Rett综合征是一种 全球每10,000-15,000名女性中就有一人患有神经发育障碍。 出生时看起来很正常，患有Rett综合征的女孩经历发育 回归并获得已使用的神经学和行为特征 以确定该疾病的诊断标准。尽管Rett综合征 通常发生零星的家族性复发表明 这是疾病的基础。有几个特征与X链接的 显性基因座包括：(1)经典表型的排他性 女性；(2)Rett综合征严重患病男性的鉴定 亲缘关系；(3)母女遗传；(4)非随机X染色体 非显性专性携带者雌性的失活模式。 来自这些罕见的复发性Rett综合征家系的排除图谱数据 将该基因定位于X染色体的远端长AM(Xq27.3-Xqter)。这个 这项建议的重点是利用 分子遗传学和细胞遗传学相结合的方法。基于他们之前的工作和 加州大学洛杉矶分校新的人类遗传学系的环境和资源，他们是 处于进行这些研究的绝佳位置。这些调查将考验 使用分子遗传学和细胞遗传学相结合的方法的三个主要假设。

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.