Research Project 1

肾脏和泌尿生殖道的疾病代表了大部分的解剖缺陷， 新生儿和幼儿，并对家庭和保健系统造成重大负担。他们 需要多次医疗，有时是手术干预;它们通常仍然是模糊的分子， 病因学;并可能是复杂的，综合征，有时危及生命的条件， 在童年和青春期表现出来。基因组技术的最新进展提供了一个独特的 有机会研究这些疾病，并提供准确和及时的诊断，在某些情况下， 帮助集中和/或重新定向医疗护理，并为有受影响儿童的家庭提供支持。 此外，这种遗传方法特别有吸引力，因为过去的研究，通常是大规模的， 家庭或广泛的队列，导致了高度渗透突变的鉴定，这反过来又 阐明了疾病的病理机制。项目1旨在利用杜克大学广泛的基础设施 儿科和新生儿诊所建立一种方法，通过它我们可以有效地利用信息 从基因组研究中获得，以改善儿童的临床评估和后续治疗。 肾脏和泌尿生殖道畸形。此外，这项研究的数据有可能帮助了解 控制泌尿生殖道发育的细胞机制，并通过传播我们的 该中心和科学界的研究结果，加强了一系列新的研究，从基础研究， 新的治疗模式的发展。我们提出两个目标。首先，我们将确定和 对50名患有综合征和非综合征的儿童的初始队列进行详细的表型表征， 综合征性先天性肾脏和泌尿道异常及其父母。二是 进行全外显子组测序，以确定潜在的致病变异，并制定最佳实践 对于临床确认的突变数据以及混合临床和研究研究的回报， 给医生足够的信心。这些研究将告知全外显子组测序在基因组中的应用。 临床环境和潜在的丰富的研究发现，为我们的中心和更广泛的社区。

Disorders of the kidney and urogenital tract represent a substantial fraction of anatomical defects in neonates and young children and pose a significant burden in families and the healthcare system. They require multiple medical, and sometimes surgical, interventions; they typically remain of obscure molecular etiology; and can be the harbinger of complex, syndromic, sometimes life-threatening conditions that manifest later in childhood and adolescence. Recent advances in genomic technologies offer a unique opportunity to study these disorders and to offer accurate and timely diagnosis that, in some instances, will help focus and/or redirect medical care, as well as provide support to families with affected children. Moreover, such genetic approaches are particularly attractive because past studies, typically on large families or extensive cohorts, have led to the identification of highly penetrant mutations, which have In turn illuminated disease pathomechanism. Project 1 aims to leverage the extensive infrastructure at the Duke Pediatric and Neonatal Clinics to establish a method by which we can utilize efficiently the information obtained from genomic studies to improve clinical evaluation and subsequent treatment of children with kidney and urogenital tract malformations. In addition, data from this study have the potential to help inform the cellular mechanisms governing genitourinary tract development and, through the dissemination of our findings both across this Center and to the scientific community, potentiate a range of new studies from basic biology to the development of new therapeutic paradigms. We propose two Aims. First, we will ascertain and perform detailed phenotypic characterization of an initial cohort of 50 children with syndromic and non- syndromic congenital anomalies of the kidney and the urinary tract and their parents. Second, we will perform whole exome sequencing to identify potential disease causing variants and to develop best practices for the return of both clinically-confirmed mutational data as well as hybrid clinical and research studies of sufficient confidence to physicians. These studies will inform the utility of whole exome sequencing in the clinical setting and potentiate rich research discovery for our Center and the broader community.