Kids First: Genetics of Kidney and Urinary Tract Malformations

The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the genomic and phenotypic data from this study are accessible through dbGaP. The data is also available at the Kids First Portal, where other Kids First datasets can also be accessed in the cloud for data analysis, data visualization, collaboration and interoperability, open to all researchers and developers.

• Study Weblinks:
  • Kids First X01 Abstracts
• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Cohort
  • Parent-Offspring Trios
• Total number of consented subjects: 147
• Subject Sample Telemetry Report (SSTR)

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 2019). 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).

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).

• Primary Phenotype: Renal Adysplasia
• Hydronephrosis
• Vesicoureteral Reflux

• BioProject
• BioSample

• Principal Investigator
  • Ali Gharavi, MD. Columbia University Health Sciences.
• Funding Source
  • X01 HL145698-01. National Institutes of Health, Bethesda, MD, USA.