Kids First: Genetics of Kidney and Urinary Tract Malformations

Congenital defects of the kidney and urinary tract are a common cause of kidney failure in children and adults and elucidation of the genetics of these disorders will provide new opportunities for diagnosis, risk stratification and prevention of complications.]]>
Around 550 trios were selected for whole genome sequencing as part of the Gabriella Miller Kids First project. Patients with congenital anomalies of the kidney and urinary tract (germline tissues), along with germline DNA from the proband's mother and father make up each trio. The trios have been collected as part of the Genetics of Chronic Kidney disease study at Columbia University, which includes international collaborators. Each trio has associated phenotypic data.]]>
Congenital malformations of the kidney and urinary tract (CAKUT) are present in 3 to 7 per 1,000 births, accounting for 23% of birth defects, and for 40-50% of pediatric and 7% of adult end-stage renal failure. CAKUT frequently occurs in conjunction with other structural birth defects and impacts long-term survival (Sanna-Cherchi et al., JCI 2018, PMID: 29293093). Studies of 57,000 children with birth defects indicated that CAKUT patients have a 40% five-year mortality, compared to 15% for all other defects combined. Over 100 different genetic disorders can cause CAKUT and together explain 15-20% of cases (Sanna-Cherchi et al., AJHG 2017, Groopman et al., NEJM 2019, PMID: 30586318). In order to understand the etiology of CAKUT, the investigators have recruited large numbers of CAKUT cases and their parents, recruited from multiple countries, over the course of many years of collaborative studies. For the current Kids First project whole genome sequencing (WGS) will be performed in 550 case-parent trios of European descent included form the USA (New York) and international sites (Poland and Italy). ]]>