A truncating NRIP1 variant in an Arabic family with congenital anomalies of the kidneys and urinary tract

Abstract

Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of early-onset chronic kidney disease. In a previous study, we identified a heterozygous truncating variant in nuclear receptor-interacting protein 1 (NRIP1) as CAKUT causing via dysregulation of retinoic acid signaling. This large family remains the only family with NRIP1 variant reported so far. Here, we describe one additional CAKUT family with a truncating variant in NRIP1. By whole-exome sequencing, we identified one heterozygous frameshift variant (p.Asn676Lysfs*27) in an isolated CAKUT patient with bilateral hydroureteronephrosis and right grade V vesicoureteral reflux (VUR) and in the affected father with left renal hypoplasia. The variant is present twice in a heterozygous state in the gnomAD database of 125,000 control individuals. We report the second CAKUT family with a truncating variant in NRIP1, confirming that loss-of-function mutations in NRIP1 are a novel monogenic cause of human autosomal dominant CAKUT.

Keywords: CAKUT; NRIP1; whole-exome sequencing.