Molecular Genetics of Inherited Focal Glomerulosclerosis

首发几种肾病综合征及局灶性节段性肾病的识别 肾小球硬化(FSGS)基因对 了解肾小球功能和疾病。然而，很明显， 已知的基因只占这些疾病的一小部分。在这里，我们的目标是 用2500多个数据库进一步阐明FSGS的遗传基础 在过去的11年里，个人聚集在一起。具体地说，我们将表演 FSGS家系和患者已知FSGS基因突变分析 有零星的FSGS。我们将继续我们正在进行的家庭查明工作 FSGS以及零星的成人和儿童病例。这些基因的突变分析 已知的FSGS基因将进一步帮助我们理解 突变，告知基因型/表型关系，提供进一步的信息 关于结构和功能，并有助于澄清基因检测的用处。我们 还将致力于识别新的FSGS基因。通过全基因组扫描，我们 已经确定了几个遗传区域，这些区域似乎含有尚未确定的 FSGS基因。我们将分析这些疾病相关区域内的基因 以识别与疾病相关的变异。我们将继续表演 在新的、遗传信息丰富的家系中进行额外的全基因组扫描 已经确定了。我们将检验这样一种假设，即稀有DNA序列变异 足细胞/肾小球关键基因与FSGS的病因学有关。我们会 300例FSGS患者和300例对照候选基因的重测序 确定这些基因中罕见的有害变异在病例中是否更常见。 我们将在独立的样本集中复制积极的结果。 FSGS是慢性肾脏疾病和肾脏的一个重要且不断增长的原因 失败了。FSGS也是各种基本条件的共同后果。 这些研究将有助于了解这种疾病的根本原因。

Identification of the first several nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) genes has had a significant impact on the understanding of glomerular function and disease. However, It is clear that the known genes account for only a fraction of these diseases. Here our goal is further elucidation of the genetic basis of FSGS, using a database of over 2500 individuals assembled over the past eleven years. Specifically, we will perform mutational analysis of known FSGS genes in families with FSGS and in patients with sporadic FSGS. We will continue our ongoing ascertainment of families with FSGS as well as sporadic adult and pediatric cases. Mutational analysis of these known FSGS genes will further inform our understanding of the spectrum of mutations, inform genotype/phenotype relationships, provide further information regarding structure and function, and help clarify the utility of genetic testing. We will also aim to Identify new FSGS genes. Through genome-wide scans, we have identified several genetic regions that appear to harbor as yet unidentified FSGS genes. We will analyze genes within these disease-associated regions in order to identify disease-associated variation. We will continue to perform additional genome-wide scans in new, genetically informative families as they are ascertained. We will test the hypothesis that rare DNA sequence variants in critical podocyte/glomerulus genes contribute to the etiology of FSGS. We will resequence candidate genes in 300 FSGS cases and 300 controls and determine if rare deleterious variants in these genes are more common in cases. We will replicate positive results in independent sample sets. FSGS is a significant and growing cause of chronic kidney disease and kidney failure. FSGS is also a common consequence of a variety of primary conditions. These studies will help understand the underlying causes of this disease.