X-LINKED MENTAL RETARDATION--LINKAGE & CLINICAL STUDIES

X连锁精神发育迟滞(XLMR)是精神障碍的主要原因 男性发育迟缓。尽管在以下方面取得了重大进展： 在过去的十年里，在理解脆弱的X的过程中，人们对 其余的X连锁疾病共同导致了60%-70%的XLMR。 虽然本提案记录了27个实体，但大多数家庭 患有XLMR的患者仍然没有明确的诊断。尽管暗示性的X- 其中几种疾病的染色体定位已有报道。 只有一次Lod得分达到显著水平。总体而言, 不能直接进行实验室诊断或产前诊断 这些家庭。 目前的调查旨在确定X连锁的家庭 智力低下(不包括脆弱的X家庭)，并映射许多 使用DNA探针和高分辨率染色体尽可能地解决这些疾病 学习。因此，这项研究将对 X染色体的连锁图谱。改善了许多人的产前诊断 这些紊乱也将是一个可能的结果。它还被设计成 确定这些临床描述中的某些实际上是否代表 同样的疾病，以及不寻常的遗传机制是否在 这群家庭。临床、神经心理学、MR 成像和其他研究将被用来进一步定义临床 以及这些障碍的行为表型。总的来说，这项研究是 计划在5年内确定40-45个家庭的特征。

X-linked mental retardation (XLMR) constitutes a major cause of mental retardation in males. Although significant progress has been made in the last decade in understanding the Fragile X, little is known of the remaining X-linked disorders which collectively cause 60-70% of XLMR. Although 27 entities are documented in the present proposal, most families with XLMR remain without a specific diagnosis. Although suggestive X- chromosomal localizations have been reported for a few of these disorders in only one instance has the lod score reached significance. In general, direct laboratory diagnosis or prenatal diagnosis is not available for these families. The present investigation is designed to ascertain families with X-linked mental retardation (excluding Fragile X families), and to map as many of these disorders as possible using DNA probes and high resolution chromosome studies. This study will, therefore, contribute significantly to the linkage map of the X chromosome. Improved prenatal diagnosis for many of these disorders will also be a likely outcome. It is also designed to determine whether certain of these clinical descriptions in fact, represent the same disorder, and whether unusual genetic mechanisms are operative in this group of families. A combination of clinical, neuropsychological, MR imaging, and other studies will be utilized to further define the clinical and behavioral phenotypes of these disorders. Overall, the study is planned to ascertain and characterize 40-45 families in 5 years.