A MULTI-CENTER STUDY TO MAP GENES FOR FUCH'S DYSTROPHY

绘制 Fuch 营养不良基因图谱的多中心研究

• 批准号: 7723442
• 负责人: SUDHA K IYENGAR
• 金额: $ 0.91万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723442
• 关键词: Affect; Biology; Blood specimen; Bullous Keratopathy; Candidate Disease Gene; Cataract Extraction; Chromosome Mapping; Clinical; Clinical Data; Computer Retrieval of Information on Scientific Projects Database; Cornea; Corneal Endothelium; Corneal dystrophy; Counseling; DNA; DNA Markers; Data; Data Collection; Databases; Descemet' s membrane; Disease; Edema; Epithelial; Esthesia; Etiology; Family; Family Study; Family history of; Foreign Bodies; Funding; Gap Junctions; Genes; Genetic; Grant; Individual; Institution; Investigation; Keratoplasty; Lead; Measures; Methods; Microscopic; Modeling; Molecular; Molecular Genetics; Mutation; Nexus (resin cement); Numbers; Online Systems; Pain; Population; Populations at Risk; Research; Research Personnel; Resources; Risk; Role; Sampling; Severities; Signal Transduction; Site; Source; Staging; Standards of Weights and Measures; Swelling; Therapeutic Intervention; United States National Institutes of Health; Vision; base; case control; genetic analysis; genetic linkage analysis; genome wide association study; indexing; insight; instrument; novel; proband; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fuchs'endothelial corneal dystrophy (FECD; MIM136800) is a common disease affecting approximately 1% of the general US population. Initially asymptomatic, individuals eventually present with decreased vision, foreign body sensation and pain upon waking. Slit lamp (microscopic) examination initially shows focal thickenings of the Descemet's membrane known as corneal guttae, with subsequent stromal edema (swelling), epithelial edema and, in advanced stages, painful bullous keratopathy. FECD is a common indication for corneal transplantation alone or in combination with cataract surgery. In addition, individuals undergoing cataract surgery with FECD are at significant risk for corneal decompensation, requiring subsequent corneal transplantation. Molecular data on the genetic basis of corneal dystrophies is limited. With a significant population at risk, the identification of the gene(s) that may contribute to the dystrophy would be very useful for counseling, implementation of standard methods for therapeutic intervention, and ultimately gene modulation and/or therapy. In this study, we propose to use the network built by the active, multi-center NEI-funded Cornea Donor Study (CDS) as the nexus to identify 500 families with FECD using the consortium model. We will identify cases with advanced FECD and characterize the extent of familial clustering using a clinical measure of severity as a semi-quantitative trait. Family history, clinical, and other demographic information will be collected using a standardized instrument. Histopathologic confirmation of advanced index cases will be obtained. Blood samples will be collected for molecular genetic analyses. A web-based database is being constructed to facilitate multi-site data collection. A genome-wide scan will be conducted utilizing DNA collected from the index cases and families (N = 500 families; estimated N = 500 sib pairs). A secondary case-control analysis will be performed utilizing the probands from the family study and matched controls (N=500 cases; N = 500 controls).Model-free linkage analysis will be conducted using the DNA marker data in conjunction with the clinical data on FECD to identify linkage signals. Candidate genes identified through previous investigations of a limited number of families (e.g. COL8A2) will be examined for mutations. Thus, we will investigate the importance of these genes on a more global basis by characterizing their role in a larger sample. We anticipate that this study will lead to novel insights into the etiology of FECD and the biology of the corneal endothelium.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 Fuchs'Odpophelial Corneal营养不良（FECD; MIM136800）是一种常见疾病，影响了大约1％的美国人群。 最初无症状的人最终会出现视力下降，外国体内感觉和醒来时的疼痛。缝隙灯（微观）检查最初显示了descemet膜的局灶性增厚，称为角膜guttae，随后的基质水肿（肿胀），上皮水肿，在晚期阶段，疼痛的乳腺癌性角膜病。 FECD是单独或与白内障手术结合的角膜移植的常见指示。 此外，接受白内障手术的个体具有角膜代偿性的很大风险，需要随后的角膜移植。关于角膜营养不良的遗传基础的分子数据有限。在有大量危险中，可能导致营养不良的基因的鉴定对于咨询，实施治疗干预的标准方法以及最终基因调节和/或治疗将非常有用。在这项研究中，我们建议使用由活跃的，多中心的Nei资助的角膜供体研究（CDS）作为Nexus建立的网络，以使用财团模型识别500个患有FECD的家庭。我们将确定具有晚期FECD的病例，并使用临床严重程度作为半定量性状的临床指标来表征家族聚类的程度。 家族史，临床和其他人口统计信息将使用标准化仪器收集。 将获得晚期指数病例的组织病理学确认。 将收集血液样本进行分子遗传分析。 正在构建基于Web的数据库，以促进多站点数据收集。将通过从指数病例和家族收集的DNA进行全基因组扫描（n = 500个家庭；估计n = 500 SIB对）。 利用家庭研究和匹配的对照组中的概率（n = 500例； n = 500个对照组），将进行次要病例对照分析。将使用与FECD上的临床数据结合使用DNA标记数据来进行无模型的链接分析，以识别链接信号。 将检查通过对有限数量的家庭（例如COL8A2）的候选基因进行突变。 因此，我们将通过表征它们在较大样本中的作用来研究这些基因的重要性。 我们预计这项研究将导致对FECD病因和角膜内皮生物学的新见解。