X-LINKED MENTAL RETARDATION: LINKAGE & CLINICAL STUDIES

X连锁智力低下：连锁

• 批准号: 2392398
• 负责人: HERBERT A LUBS
• 金额: $ 61.58万
• 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/2392398
• 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.

X连锁精神发育迟滞（XLMR）是最常见的原因 男性遗传性智力迟钝的主要病因 在已知的25- 50%的弱智男性超过弱智的作用 女性已知有127种XLMR疾病。五十- 三种具有非特异性XLMR的疾病或家族已在区域性 并克隆了15个XLMR基因。编写本 这项研究是为了更好地描述他们的临床和神经行为 表型，影响这些参数之间的相关性，地图额外 XLMR综合征和非特异性疾病，并进一步缩小其 这样就可以克隆更多的基因。 在研究的前五年，28个XLMR综合征和19个家族 与非特异性XLMR的关系进行了研究。共有62个家庭 入组研究; 34例具有实际或预计Lod评分 超过2.0。10个新的综合征或非特异性XLMR家系 已经描述了局部化，并且已经描述了七种综合征， 重大重新定义。总共有十个新的本地化， 影响。更好的本地化已经完成了两个额外的 紊乱 在未来五年的研究中，计划再包括25个 具有特异性综合征或非特异性XLMR的大家族， 联系研究。较小的家庭也将被纳入联系 如果他们有一个特定的综合征，或排除映射，如果 分类为非特异性。至少有四个基因将被克隆：艾伦- Herndon-Dudley综合征（Xq 21）; Mohr-Tranebjaerg综合征（Xq 22）; Snyder-Robinson综合征（Xp21.2- p22.2）和MR基因定位于 Xq 12在1000 kb缺失。超过90个家庭将被纳入 在十年的时间里学习。该研究是一个合作项目 迈阿密大学格林伍德基因中心 位于盖恩斯维尔和凯斯西储大学的佛罗里达， 成为绘制XLMR疾病的国际合作的一部分。