Research Project 1

点击翻译按钮获取中文摘要

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