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

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...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part A 2022-01, Vol.188 (1), p.310-313
Main Authors: Zheng, Bixia, Wang, Chunyan, Seltzsam, Steve, Schneider, Sophia, Schierbaum, Luca, Wu, Wilfred, Dai, Rufeng, Connaughton, Dervla M., Nakayama, Makiko, Mann, Nina, Bauer, Stuart B., Awad, Hazem S., Eid, Loai A., Tasic, Velibor, Shril, Shirlee, Hildebrandt, Friedhelm
Format: Article
Language:English
Subjects:
Arabs
CAKUT
Congenital defects
Exome Sequencing
Humans
Hypoplasia
Kidney - abnormalities
Kidney diseases
Kidneys
NRIP1
Nuclear Receptor Interacting Protein 1 - genetics
Retinoic acid
Urinary Tract
Urogenital Abnormalities - diagnosis
Urogenital Abnormalities - genetics
Urogenital system
Vesico-Ureteral Reflux - genetics
whole‐exome sequencing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.62502