MOLECULAR GENETICS OF FACIO AUDIO SYMPHALANGISM

描述(取自应用程序) 面部-音频-交叉症是一种常染色体显性遗传性疾病 以三重发现为特征的，包括明显的相，早发 耳聋和渐进性关节融合。我们发现了一名体型庞大的夏威夷人 有这种障碍的家庭。此项目的目标是定义 疾病的表型和自然病史，决定染色体 定位缺陷基因并鉴定缺陷基因。对这件事 最后，该提案的具体目标是：1)定义临床 面-耳-指畸形的表型和自然病史。我们会 描述临床和放射学表现，以及自然的 这个多代大家庭的病史。2)至 确定缺陷基因的染色体位置。使用记号笔 在候选基因和全基因组标记中，我将使用连锁研究 确定含有致病基因的染色体区域。3)至 确定面-耳-指畸形是否存在基因座异质性 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。通过对其他对象执行连锁分析 面部-音频-交叉症家系我会确定是否有超过 1个Fas病基因。我还将在家庭中开展联系研究 伴有相关疾病，包括多发性融合综合征和近端 共同定位，以确定疾病基因是否与Fas共定位。4) 目的：确定面-耳-指畸形的致病基因。按位置设置 策略，将从Fas区间分离候选基因。突变 分析将用于确定Fas中的缺陷基因。这个项目 代表了一种遗传学方法来剖析鲜为人知的 发展和维护关节的完整性。身份的识别 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，并在这方面刺激了生物学研究 区域。

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.