X-LINKED MENTAL RETARDATION: LINKAGE & CLINICAL STUDIES

X连锁智力低下：连锁

• 批准号: 2673599
• 负责人: HERBERT A LUBS
• 金额: $ 63.28万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673599
• 关键词: clinical research; developmental neurobiology; family genetics; gender difference; gene mutation; genetic markers; human genetic material tag; human population genetics; human subject; linkage mapping; male; mental retardation; molecular cloning; neuropsychological tests; phenotype; sex linked trait; syndrome

DESCRIPTION: X-linked mental retardation (XLMR) is the most common cause of inherited mental retardation in males and plays a major etiologic role in the known 25-50 percent excess of retarded males over retarded females. One hundred and twenty-seven XLMR disorders are known. Fifty- three disorders or families with nonspecific XLMR have been regionally mapped and 15 XLMR genes have been cloned. The purpose of the present study is to better characterize their clinical and neurobehavioral phenotype, effect correlations between these parameters, map additional XLMR syndromes and nonspecific disorders, and to further narrow their localizations so that it will become possible to clone additional genes. In the first five years of the study, 28 XLMR syndromes and 19 families with nonspecific XLMR have been studied. A total of 62 families have been entered into the study; 34 have an actual or projected Lod score over 2.0. Ten new syndromes or nonspecific XLMR families with gene localizations have been described and seven syndromes have been significantly redefined. A total of ten new localizations have been effected. Better localization has been accomplished in two additional disorders. In the next five years of the study it is planned to include 25 more large families with either specific syndromes or nonspecific XLMR for linkage studies. Smaller families will also be included for linkage studies if they have a specific syndrome, or for exclusion mapping, if classified as nonspecific. At least four genes will be cloned: Allan- Herndon-Dudley syndrome (Xq21); Mohr-Tranebjaerg syndrome (Xq22); Snyder-Robinson syndrome (Xp21.2- p22.2) and a gene for MR localized to Xq12 in a 1000 kb deletion. Over 90 families will be included in the study over the ten year period. The study is a collaborative project between the University of Miami, Greenwood Genetic Center, University of Florida in Gainesville and Case Western Reserve University, and will be part of an international collaboration for mapping XLMR disorders.

描述：X连锁的智力低下（XLMR）是最常见的原因 男性遗传性智力低下，并发挥了主要的病因 在已知的25-50％过量的智障男性中的角色超过了智障 女性。已知一百二十七个XLMR疾病。五十- 三种疾病或非特异性XLMR的家庭在区域上是 映射和15个XLMR基因已克隆。现在的目的 研究是为了更好地描述其临床和神经行为 表型，这些参数之间的效果相关性，映射附加 XLMR综合征和非特异性疾病，并进一步缩小其 本地化，以便可以克隆其他基因。 在研究的头五年中，有28个XLMR综合征和19个家庭 使用非特异性XLMR进行了研究。共有62个家庭 已进入研究； 34具有实际或预计的LOD分数 超过2.0。具有基因的十种新综合征或非特异性XLMR家族 已经描述了本地化，七个综合症已经 重新定义。总共十个新的本地化已经 实现。在另外两个方面已经完成了更好的本地化 疾病。 在研究的接下来的五年中，计划将包括25个 患有特定综合征或非特异性XLMR的大家庭 连锁研究。较小的家庭也将包括在内 研究他们是否患有特定综合征，或用于排除映射 分类为非特异性。至少要克隆四个基因：allan- Herndon-Dudley综合征（XQ21）; Mohr-Tranebjaerg综合征（XQ22）; Snyder-Robinson综合征（XP21.2- P22.2）和MR局部的基因 XQ12在1000 kb删除中。超过90个家庭将包括 在十年期间学习。该研究是一个协作项目 在迈阿密大学，格林伍德遗传中心，大学 盖恩斯维尔（Gainesville）和凯斯（Case Western Reserve University）的佛罗里达州，将 成为映射XLMR疾病的国际合作的一部分。