MOLECULAR GENETICS OF FACIO AUDIO SYMPHALANGISM

描述（取自应用程序） 面听性指关节炎是一种常染色体显性遗传病 特征为三联征，包括不同的相，早发性 耳聋和进行性关节融合。 我们发现了一个夏威夷大块头 家庭与这种疾病。 本项目的目标是定义 表型和疾病的自然史，决定染色体 定位缺陷基因并鉴定缺陷基因。 本 最后，建议的具体目标是：1）定义临床 表型和自然病史的面-听-趾畸形。 我们将 描述临床和放射学发现以及自然的 在这个多代同堂的大家庭中的疾病史。 2)到 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 以确定包含疾病基因的染色体区域。 3)到 确定面-听-指畸形是否存在位点异质性， 如果其他表型相似的显性遗传疾病映射到 相同的染色体位置 通过对其他人进行连锁分析， 面-听-指关节综合征的家庭，我将确定是否有超过 一个FAS疾病基因。 我还将在家庭中进行联系研究 伴有相关疾病，包括多发性骨结合综合征和近端 指关节粘连，以确定疾病基因是否与FAS共定位。 四、 确定面-听-指畸形的致病基因。 由位置 策略，将分离来自FAS区间的候选基因。 突变 分析将用于鉴定FAS中的缺陷基因。 这个项目 代表了一种遗传学的方法来剖析人们知之甚少的 发展和保持关节的完整性。 识别 参与这一过程的基因将提供识别其他基因的手段 参与了这一复杂的途径，并刺激了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.