Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract

Daw Yang Hwang, Gabriel C. Dworschak, Stefan Kohl, Pawaree Saisawat, Asaf Vivante, Alina C. Hilger, Heiko M. Reutter, Neveen A. Soliman, Radovan Bogdanovic, Elijah O. Kehinde, Velibor Tasic, Friedhelm Hildebrandt

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease. CAKUT can be caused by monogenic mutations; however, data are lacking on their frequency. Genetic diagnosis has been hampered by genetic heterogeneity and lack of genotype-phenotype correlation. To determine the percentage of cases with CAKUT that can be explained by mutations in known CAKUT genes, we analyzed the coding exons of the 17 known dominant CAKUT-causing genes in a cohort of 749 individuals from 650 families with CAKUT. The most common phenotypes in this CAKUT cohort were vesicoureteral reflux in 288 patients, renal hypodysplasia in 120 patients, and unilateral renal agenesis in 90 patients. We identified 37 different heterozygous mutations (33 novel) in 12 of the 17 known genes in 47 patients from 41 of the 650 families (6.3%). These mutations include (number of families): BMP7 (1), CDC5L (1), CHD1L (5), EYA1 (3), GATA3 (2), HNF1B (6), PAX2 (5), RET (3), ROBO2 (4), SALL1 (9), SIX2 (1), and SIX5 (1). Furthermore, several mutations previously reported to be disease-causing are most likely benign variants. Thus, in a large cohort over 6% of families with isolated CAKUT are caused by a mutation in 12 of 17 dominant CAKUT genes. Our report represents one of the most in-depth diagnostic studies of monogenic causes of isolated CAKUT in children.

Original languageEnglish
Pages (from-to)1429-1433
Number of pages5
JournalKidney International
Volume85
Issue number6
DOIs
Publication statusPublished - Jun 2014

Keywords

  • genetic renal disease
  • renal agenesis
  • renal development

ASJC Scopus subject areas

  • Nephrology

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