MOLECULAR GENETICS OF FACIO AUDIO SYMPHALANGISM

描述（取自申请） 面音交联症 (FAS) 是一种常染色体显性遗传疾病 其特点是具有三重表现，包括不同的面貌、早发 耳聋和进行性关节融合。 我们发现了一个大型夏威夷 患有这种疾病的家庭。 该项目的目标是定义 疾病的表型和自然史，确定染色体 定位缺陷基因并识别缺陷基因。 对此 最后，该提案的具体目标是： 1）定义临床 facio-audio-symphalangism 的表型和自然史。 我们会 描述临床和放射学结果以及自然情况 这个多代大家庭的疾病史。 2) 至 确定缺陷基因的染色体位置。 使用标记 在候选基因和全基因组标记中，我将使用连锁研究 以确定含有疾病基因的染色体区域。 3) 至 确定 facio-audio-symphalangism 中是否存在位点异质性，以及 如果其他表型相似的显性遗传性疾病映射到 相同的染色体位置。 通过对其他对象进行连锁分析 facio-audio-symphalangism 家族我将确定是否有超过 一种 FAS 疾病基因。 我还将在家庭中进行联系研究 患有相关疾病，包括多发性骨连接综合征和近端骨连接综合征 symphalangism，以确定疾病基因是否与 FAS 共定位。 4） 识别面音交感中的疾病基因。 通过位置 策略，来自FAS区间的候选基因将被分离出来。 突变 分析将用于识别 FAS 中的缺陷基因。 这个项目 代表了一种遗传学方法来剖析人们知之甚少的过程 发展和维护联合诚信。 识别一个 参与该过程的基因将提供识别其他基因的方法 参与这一复杂的途径并刺激这方面的生物学研究 区。

DESCRIPTION (taken from application) Facio-audio-symphalangism (FAS) is an autosomal dominant disorder characterized by a triad of findings including distinct facies, early onset deafness and progressive joint fusions. We have identified a large Hawaiian family with this disorder. The goal of this project is to define the phenotype and natural history of the disease, determine the chromosomal location of the defective gene and identify the defective gene. To this end, the specific aims of the proposal are: 1) To define the clinical phenotype and natural history of facio-audio-symphalangism. We will delineate the clinical and radiographic findings as well as the natural history of the disorder in this large, multigeneration family. 2) To determine the chromosomal location of the defective gene. Employing markers in both candidate genes and genome wide markers, I will use linkage studies to determine the chromosomal region containing the disease gene. 3) To determine if there is locus heterogeneity in facio-audio-symphalangism and if other phenotypically similar dominantly inherited disorders map to the same chromosomal location. By performing linkage analysis on other facio-audio-symphalangism families I will determine if there is more than one FAS disease gene. I will also carry out linkage studies in families with related disorders, including multiple synostoses syndrome and proximal symphalangism, to determine if the disease genes co-localize with FAS. 4) To identify the disease gene in facio-audio-symphalangism. By a positional strategy, candidate genes from the FAS interval will be isolated. Mutation analysis will be used to identify the defective gene in FAS. This project represents a genetic approach to dissecting the poorly understood process of the development and maintenance of joint integrity. Identification of a gene involved in this process will provide the means to identify other genes involved in this complex pathway and stimulate biologic research in this area.