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. 2023 Jun;31(6):674-680.
doi: 10.1038/s41431-023-01331-x. Epub 2023 Mar 16.

Exome sequencing in individuals with congenital anomalies of the kidney and urinary tract (CAKUT): a single-center experience

Korbinian M Riedhammer  1   2 , Jasmina Ćomić  1   2 , Velibor Tasic  3 , Jovana Putnik  4 , Nora Abazi-Emini  3 , Aleksandra Paripovic  4 , Natasa Stajic  4 , Thomas Meitinger  1 , Valbona Nushi-Stavileci  5 , Riccardo Berutti  1 , Matthias C Braunisch  2 , Julia Hoefele  6
Affiliations

Exome sequencing in individuals with congenital anomalies of the kidney and urinary tract (CAKUT): a single-center experience

Korbinian M Riedhammer et al. Eur J Hum Genet. 2023 Jun.

Abstract

Individuals with congenital anomalies of the kidney and urinary tract (CAKUT) show a broad spectrum of malformations. CAKUT can occur in an isolated fashion or as part of a syndromic disorder and can lead to end-stage kidney failure. A monogenic cause can be identified in ~12% of affected individuals. This study investigated a single-center CAKUT cohort analyzed by exome sequencing (ES). Emphasis was placed on the question whether diagnostic yield differs between certain CAKUT phenotypes (e.g., bilateral kidney affection, unilateral kidney affection or only urinary tract affection). 86 unrelated individuals with CAKUT were categorized according to their phenotype and analyzed by ES to identify a monogenic cause. Prioritized variants were rated according to the recommendations of the American College of Medical Genetics and Genomics and the Association for Clinical Genomic Science. Diagnostic yields of different phenotypic categories were compared. Clinical data were collected using a standardized questionnaire. In the study cohort, 7/86 individuals had a (likely) pathogenic variant in the genes PAX2, PBX1, EYA1, or SALL1. Additionally, in one individual, a 17q12 deletion syndrome (including HNF1B) was detected. 64 individuals had a kidney affection, which was bilateral in 36. All solved cases (8/86, 9%) had bilateral kidney affection (diagnostic yield in subcohort: 8/36, 22%). Although the diagnostic yield in CAKUT cohorts is low, our single-center experience argues, that, in individuals with bilateral kidney affection, monogenic burden is higher than in those with unilateral kidney or only urinary tract affection.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Cohort overview according to renal and urinary tract phenotype (two-step process, see Methods section).
This figure was created with the free web-based tool SankeyMATIC (http://sankeymatic.com/build/). CAKUT congenital anomalies of the kidney and urinary tract, VUR vesicoureteral reflux.
Fig. 2
Fig. 2. Distribution of solved cases in the CAKUT cohort consisting of 86 index cases grouped according to broader phenotype categories.
Solved cases are those in which a genetic diagnosis could be made by exome sequencing.
See this image and copyright information in PMC

References

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