X-LINKED MENTAL RETARDATION: LINKAGE & CLINICAL STUDIES

X连锁智力低下：连锁

• 批准号: 2888990
• 负责人: HERBERT A LUBS
• 金额: $ 61.81万
• 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/2888990
• 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 连锁智力低下 (XLMR) 是最常见的原因 是男性遗传性智力低下的一个重要病因 已知男性智障人数比智障男性多出 25-50% 女性。已知有一百二十七种 XLMR 疾病。五十- 三种患有非特异性 XLMR 的疾病或家族已在区域内 映射并克隆了 15 个 XLMR 基因。目前的目的 研究是为了更好地表征他们的临床和神经行为 表型，这些参数之间的效应相关性，地图附加 XLMR 综合征和非特异性疾病，并进一步缩小其范围 定位，以便克隆额外的基因成为可能。 在研究的前五年中，28 个 XLMR 综合征和 19 个家庭 已对非特异性 XLMR 进行了研究。共有62户家庭拥有 已进入研究； 34 拥有实际或预计的 Lod 分数 2.0以上。十个新的综合征或非特异性 XLMR 基因家族 已描述了定位并已描述了七种综合症 显着重新定义。总共有十个新的本地化版本 生效了。另外两个地方已经完成了更好的本地化 失调。 在未来五年的研究中，计划纳入 25 个以上 患有特定综合征或非特异性 XLMR 的大家庭 联系研究。较小的家庭也将被纳入联系范围 研究他们是否有特定的综合症，或者进行排除映射，如果 归类为非特异性。至少有四个基因将被克隆：Allan- 赫恩登-达德利综合征 (Xq21)； Mohr-Tranebjaerg 综合征 (Xq22)； Snyder-Robinson 综合征 (Xp21.2- p22.2) 和 MR 基因定位于 1000 kb 删除中的 Xq12。超过90个家庭将被纳入其中 历时十年的学习。该研究是一个合作项目 迈阿密大学、格林伍德遗传中心、大学之间 佛罗里达州盖恩斯维尔和凯斯西储大学，并将 参与绘制 XLMR 疾病图谱的国际合作。