Identification of CAKUT-associated genes using a worldwide patient-cohort and high-throughput methods for genetic analysis

使用全球患者队列和高通量遗传分析方法鉴定 CAKUT 相关基因

• 批准号: 283748340
• 负责人: Dr. Amelie van der Ven
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/283748340?language=en
• 关键词: Identification; CAKUT; associated; genes; using

Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT) comprise a large spectrum of pathological conditions. CAKUT contribute to 50% of terminal kidney diseases during the first two decades of life and often necessitate cost-intensive kidney-replacement-therapies in the long term. CAKUT are currently believed to develop predominantly based on abnormalities in the DNA of the affected. However, until today only a small fraction of disease-related genes has successfully been identified and functionally characterized. Dr. Hildebrandt (HHMI, Boston Childrens Hospital, Harvard Medical School) has established a diagnostic approach for the efficient identification of CAKUT-associated genes in his laboratory. Throughout the next few years, the applicant is planning to apply these high-throughput methods for genetic analysis (e.g. homozygosity mapping, whole exome sequencing) to his existing, world-wide cohort of 2,400 families with CAKUT. The applicant will furthermore utilize the methods to analyze the DNA of an own cohort consisting of nearly 150 patients with anorectal malformations and associated CAKUT. In the long term, there is hope that a successful identification of an increasing number of CAKUT-genes can contribute to a better understanding of disease-associated molecular pathways and the pathophysiology of CAKUT overall.

先天性肾脏和尿路异常（CAKUT）包括广泛的病理条件。在生命的头20年里，有50%的终末期肾脏疾病是由ckut引起的，从长远来看，这往往需要成本高昂的肾脏替代疗法。目前认为，CAKUT的发展主要是基于受影响的DNA异常。然而，直到今天，只有一小部分疾病相关基因被成功地识别和功能表征。Hildebrandt博士（HHMI，波士顿儿童医院，哈佛医学院）在他的实验室建立了一种有效识别cakut相关基因的诊断方法。在接下来的几年里，申请人计划将这些高通量的遗传分析方法（如纯合子作图，全外显子组测序）应用到他现有的2,400个全球CAKUT家庭队列中。申请人将进一步利用该方法分析自己的近150名肛肠畸形和相关CAKUT患者的DNA。从长远来看，成功鉴定越来越多的CAKUT基因有望有助于更好地了解疾病相关的分子途径和CAKUT的病理生理。

项目成果

Whole-Exome Sequencing Reveals FAT4 Mutations in a Clinically Unrecognizable Patient with Syndromic CAKUT: A Case Report

全外显子组测序揭示了临床无法识别的 CAKUT 综合征患者的 FAT4 突变：病例报告

• DOI: 10.1159/000477750
• 发表时间: 2017
• 期刊: Molecular Syndromology
• 影响因子: 1.1
• 作者: van der Ven;Amelie T;Shirlee;Vivante;Daw-Yang;Laricchia;Kristen M;Monkol;Velibor;Hildebrandt;Friedhelm
• 通讯作者: Friedhelm