MOLECULAR GENETICS OF FACIO AUDIO SYMPHALANGISM

FACIO 音频对称性的分子遗传学

• 批准号: 2888729
• 负责人: Deborah Krakow
• 金额: $ 6.73万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888729
• 关键词: clinical research; complementary DNA; conductive hearing loss; disease /disorder onset; family genetics; gene mutation; human genetic material tag; human subject; joint disorder; linkage mapping; molecular genetics; pathologic process; site directed mutagenesis; syndrome; clinical research; complementary DNA; conductive hearing loss; disease /disorder onset; family genetics; gene mutation; human genetic material tag; human subject; joint disorder; linkage mapping; molecular genetics; pathologic process; site directed mutagenesis; syndrome

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.

描述（取自应用程序） Facio-Audio-Smphalangism（FAS）是一种常染色体显性疾病 以一系列发现的特征，包括不同的相 耳聋和进行性关节融合。 我们已经确定了一个大夏威夷人 患有这种疾病的家庭。 该项目的目的是定义 疾病的表型和自然史，确定染色体 缺陷基因的位置并识别缺陷基因。 对此 最后，提案的具体目的是：1）定义临床 面板 - 响应式法的表型和自然历史。 我们将 描述临床和影像学发现以及自然 在这个大型多元家庭中，这种疾病的历史。 2）到 确定缺陷基因的染色体位置。 采用标记 在候选基因和基因组宽标记中，我将使用连锁研究 确定含有疾病基因的染色体区域。 3）到 确定面部原告 - 响应法中是否存在基因座异质性和 如果其他表型相似的遗传疾病映射到 相同的染色体位置。 通过对其他 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 与相关的疾病，包括多个平均综合征和近端 交响乐，以确定疾病基因是否与FAS共定位。 4） 鉴定面部原告 - 伴朗主义中的疾病基因。 由位置 策略，将分离出FAS间隔的候选基因。 突变 分析将用于识别FAS中的缺陷基因。 这个项目 代表了一种剖析熟悉的过程的遗传方法 联合完整性的发展和维护。 识别 参与此过程的基因将提供识别其他基因的手段 参与这一复杂途径并刺激生物学研究 区域。