X-LINKED MENTAL RETARDATION: LINKAGE & CLINICAL STUDIES

描述：X连锁智力低下(XLMR)是最常见的原因 遗传性智力低下在男性中是一个主要的病因 已知的智障男性超过智障男性25%-50%的原因 女性。已知的XLMR疾病有127种。五十- 三个患有非特异性XLMR的疾病或家族已经被地区性地 已定位并克隆了15个XLMR基因。现在的目的是 研究是为了更好地描述他们的临床和神经行为 表型，这些参数之间的效应相关性，MAP附加 XLMR综合征和非特异性疾病，并进一步缩小其 定位，这样就有可能克隆更多的基因。 在研究的前五年，XLMR综合征28个，19个家系 对非特异性XLMR进行了研究。共有62个家庭获得了 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10个新综合征或非特异性XLMR家系 已经描述了定位，并描述了七种综合征 大大重新定义了。总共有十个新的本地化版本 已生效。更好的本地化已经在另外两个方面完成了 精神错乱。 在未来五年的研究中，计划再纳入25个 具有特定症状或非特定XLMR的大家族 连锁研究。较小的家庭也将被包括在内进行联系 研究他们是否有特定的综合症，或进行排除映射，如果 归类为非特定的。至少将克隆四个基因：Allan- Herndon-Dudley综合征(Xq21)、Mohr-Traebjerg综合征(Xq22)； Snyder-Robinson综合征(Xp21.2-p22.2)与MR基因定位 Xq12，大小为1000kb。超过90个家庭将被包括在 在十年时间里学习。这项研究是一个合作项目 在迈阿密大学、格林伍德遗传中心、大学 在盖恩斯维尔和凯斯西部储备大学的佛罗里达大学，并将 成为绘制XLMR疾病地图的国际合作的一部分。

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.