Copy Number Variation Analysis Facilitates Identification of Genetic Causation in Patients with Congenital Anomalies of the Kidney and Urinary Tract.
BAF, B allele frequency
CAKUT, Congenital anomalies of the kidneys and urinary tract
CNV, Copy number variations
Congenital anomalies of the kidney and urinary tract
Copy number variation
GD-CNV, Genomic disorders copy number variation
IRB, Institutional review board
Monogenic disease causation
Renal developmental
Vesicoureteral reflux
WES, Whole-exome sequencing
Whole-exome sequencing
Journal
European urology open science
ISSN: 2666-1683
Titre abrégé: Eur Urol Open Sci
Pays: Netherlands
ID NLM: 101771568
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
accepted:
10
08
2022
entrez:
3
10
2022
pubmed:
4
10
2022
medline:
4
10
2022
Statut:
epublish
Résumé
Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease among children and adults younger than 30 yr. In our previous study, whole-exome sequencing (WES) identified a known monogenic cause of isolated or syndromic CAKUT in 13% of families with CAKUT. However, WES has limitations and detection of copy number variations (CNV) is technically challenging, and CNVs causative of CAKUT have previously been detected in up to 16% of cases. To detect CNVs causing CAKUT in this WES cohort and increase the diagnostic yield. We performed a genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on the same CAKUT cohort for whom WES was previously conducted. We evaluated and classified the CNVs using previously published predefined criteria. In a cohort of 170 CAKUT families, we detected a pathogenic CNV known to cause CAKUT in nine families (5.29%, 9/170). There were no competing variants on genome-wide CNV analysis or WES analysis. In addition, we identified novel likely pathogenic CNVs that may cause a CAKUT phenotype in three of the 170 families (1.76%). CNV analysis in this cohort of 170 CAKUT families previously examined via WES increased the rate of diagnosis of genetic causes of CAKUT from 13% on WES to 18% on WES + CNV analysis combined. We also identified three candidate loci that may potentially cause CAKUT. We conducted a genetics study on families with congenital anomalies of the kidney and urinary tract (CAKUT). We identified gene mutations that can explain CAKUT symptoms in 5.29% of the families, which increased the percentage of genetic causes of CAKUT to 18% from a previous study, so roughly one in five of our patients with CAKUT had a genetic cause. These analyses can help patients with CAKUT and their families in identifying a possible genetic cause.
Sections du résumé
Background
UNASSIGNED
Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease among children and adults younger than 30 yr. In our previous study, whole-exome sequencing (WES) identified a known monogenic cause of isolated or syndromic CAKUT in 13% of families with CAKUT. However, WES has limitations and detection of copy number variations (CNV) is technically challenging, and CNVs causative of CAKUT have previously been detected in up to 16% of cases.
Objective
UNASSIGNED
To detect CNVs causing CAKUT in this WES cohort and increase the diagnostic yield.
Design setting and participants
UNASSIGNED
We performed a genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on the same CAKUT cohort for whom WES was previously conducted.
Outcome measurements and statistical analysis
UNASSIGNED
We evaluated and classified the CNVs using previously published predefined criteria.
Results and limitations
UNASSIGNED
In a cohort of 170 CAKUT families, we detected a pathogenic CNV known to cause CAKUT in nine families (5.29%, 9/170). There were no competing variants on genome-wide CNV analysis or WES analysis. In addition, we identified novel likely pathogenic CNVs that may cause a CAKUT phenotype in three of the 170 families (1.76%).
Conclusions
UNASSIGNED
CNV analysis in this cohort of 170 CAKUT families previously examined via WES increased the rate of diagnosis of genetic causes of CAKUT from 13% on WES to 18% on WES + CNV analysis combined. We also identified three candidate loci that may potentially cause CAKUT.
Patient summary
UNASSIGNED
We conducted a genetics study on families with congenital anomalies of the kidney and urinary tract (CAKUT). We identified gene mutations that can explain CAKUT symptoms in 5.29% of the families, which increased the percentage of genetic causes of CAKUT to 18% from a previous study, so roughly one in five of our patients with CAKUT had a genetic cause. These analyses can help patients with CAKUT and their families in identifying a possible genetic cause.
Identifiants
pubmed: 36185583
doi: 10.1016/j.euros.2022.08.004
pii: S2666-1683(22)00874-6
pmc: PMC9520493
doi:
Types de publication
Journal Article
Langues
eng
Pagination
106-112Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK078226
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK133940
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2022 The Authors.
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