Exome analysis links kidney malformations to developmental disorders and reveals causal genes

Hila Milo Rasouly (), Sarath Babu Krishna Murthy, Natalie Vena, Gundula Povysil, Andrew Beenken, Miguel Verbitsky, Shirlee Shril, Iris Lekkerkerker, Sandy Yang, Atlas Khan, David Fasel, Janewit Wongboonsin, Jeremiah Martino, Juntao Ke, Naama Elefant, Nikita Tomar, Ofek Harnof, Sergey Kisselev, Shiraz Bheda, Sivan Reytan-Miron, Tze Y. Lim, Anna Jamry-Dziurla, Francesca Lugani, Jun Y. Zhang, Maddalena Marasa, Victoria Kolupaeva, Emily E. Groopman, Gina Jin, Iman Ghavami, Kelsey O. Stevens, Arielle C. Coughlin, Byum Hee Kil, Debanjana Chatterjee, Drew Bradbury, Jason Zheng, Karla Mehl, Maria Morban, Rachel Reingold, Stacy Piva, Xueru Mu, Adele Mittrori, Agnieszka Szmigielska, Aleksandra Gliwińska, Andrea Ranghino, Andrew S. Bomback, Andrzej Badenski, Anna Latos-Bielenska, Valentina Capone, Anna Materna-Kiryluk, Antonio Amoroso, Claudia Izzi, Claudio La Scola, David Jonathan Cohen, Domenico Santoro, Dorota Drozdz, Enrico Fiaccadori, Fangming Lin, Francesco Scolari, Francesco Tondolo, Gaetano La Manna, Gerald B. Appel, Gian Marco Ghiggeri, Gianluigi Zaza, Giovanni Montini, Giuseppe Masnata, Grażyna Krzemien, Isabella Pisani, Jai Radhakrishnan, Katarzyna Zachwieja, Loreto Gesualdo, Luigi Biancone, Davide Meneghesso, Malgorzata Mizerska-Wasiak, Marcin Tkaczyk, Marcin Zaniew, Maria K. Borszewska-Kornacka, Maria Szczepanska, Marijan Saraga, Maya K. Rao, Monica Bodria, Monika Miklaszewska, Natalie S. Uy, Olga Baraldi, Omar Bjanid, Pasquale Esposito, Pasquale Zamboli, Pierluigi Marzuillo, Pietro A. Canetta, Przemyslaw Sikora, Rik Westland, Russell J. Crew, Shumyle Alam, Stefano Guarino, Susanna Negrisolo, Thomas Hays, Shrikant Mane, Valeria Grandinetti, Velibor Tasic, Vladimir J. Lozanovski, Yasar Caliskan, David Goldstein, Richard P. Lifton, Iuliana Ionita-Laza, Krzysztof Kiryluk, Albertien M. van Eerde, Friedhelm Hildebrandt, Simone Sanna-Cherchi and Ali G. Gharavi ()
Additional contact information
Hila Milo Rasouly: Columbia University Medical Center
Sarath Babu Krishna Murthy: Columbia University Medical Center
Natalie Vena: Columbia University Medical Center
Gundula Povysil: Columbia University Medical Center
Andrew Beenken: Columbia University Medical Center
Miguel Verbitsky: Columbia University Medical Center
Shirlee Shril: Harvard Medical School
Iris Lekkerkerker: University Medical Center Utrecht
Sandy Yang: Columbia University Medical Center
Atlas Khan: Columbia University Medical Center
David Fasel: Columbia University Medical Center
Janewit Wongboonsin: Mahidol University
Jeremiah Martino: Columbia University Medical Center
Juntao Ke: Columbia University Medical Center
Naama Elefant: Columbia University Medical Center
Nikita Tomar: Columbia University Medical Center
Ofek Harnof: Columbia University Medical Center
Sergey Kisselev: Columbia University Medical Center
Shiraz Bheda: Columbia University Medical Center
Sivan Reytan-Miron: Columbia University Medical Center
Tze Y. Lim: Columbia University Medical Center
Anna Jamry-Dziurla: Poznan University of Medical Sciences
Francesca Lugani: Istituto Giannina Gaslini
Jun Y. Zhang: Columbia University Medical Center
Maddalena Marasa: Columbia University Medical Center
Victoria Kolupaeva: Columbia University Medical Center
Emily E. Groopman: Columbia University Medical Center
Gina Jin: Columbia University Medical Center
Iman Ghavami: Columbia University Medical Center
Kelsey O. Stevens: Columbia University Medical Center
Arielle C. Coughlin: Columbia University Medical Center
Byum Hee Kil: Columbia University Medical Center
Debanjana Chatterjee: Columbia University Medical Center
Drew Bradbury: Columbia University Medical Center
Jason Zheng: Columbia University Medical Center
Karla Mehl: Columbia University Medical Center
Maria Morban: Columbia University Medical Center
Rachel Reingold: Columbia University Medical Center
Stacy Piva: Columbia University Medical Center
Xueru Mu: Columbia University Medical Center
Adele Mittrori: Columbia University Medical Center
Agnieszka Szmigielska: Medical University of Warsaw
Aleksandra Gliwińska: Medical University of Silesia
Andrea Ranghino: Azienda Ospedaliera Universitaria delle Marche
Andrew S. Bomback: Columbia University Medical Center
Andrzej Badenski: Medical University of Silesia
Anna Latos-Bielenska: Poznan University of Medical Sciences
Valentina Capone: Ospedale Maggiore Policlinico
Anna Materna-Kiryluk: Poznan University of Medical Sciences
Antonio Amoroso: University of Turin
Claudia Izzi: University of Brescia and Spedali Civili
Claudio La Scola: IRCCS Azienda Ospedaliero-Universitaria di Bologna
David Jonathan Cohen: Columbia University Medical Center
Domenico Santoro: University of Messina
Dorota Drozdz: Jagiellonian University Medical College
Enrico Fiaccadori: Parma University Hospital
Fangming Lin: Columbia University Medical Center
Francesco Scolari: Spedali Civili and University
Francesco Tondolo: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Gaetano La Manna: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Gerald B. Appel: Columbia University Medical Center
Gian Marco Ghiggeri: Istituto Giannina Gaslini
Gianluigi Zaza: University of Calabria
Giovanni Montini: Ospedale Maggiore Policlinico
Giuseppe Masnata: ARNAS Brotzu Hospital
Grażyna Krzemien: Medical University of Warsaw
Isabella Pisani: Jagiellonian University Medical College
Jai Radhakrishnan: Columbia University Medical Center
Katarzyna Zachwieja: University of Messina
Loreto Gesualdo: University of Bari Aldo Moro
Luigi Biancone: University of Torino
Davide Meneghesso: Hospital University of Padova
Malgorzata Mizerska-Wasiak: Medical University of Warsaw
Marcin Tkaczyk: Polish Mother’s Memorial Hospital Research Institute
Marcin Zaniew: University of Zielona Góra
Maria K. Borszewska-Kornacka: Medical University of Silesia in Katowice
Maria Szczepanska: Medical University of Silesia
Marijan Saraga: School of Medicine
Maya K. Rao: Columbia University Medical Center
Monica Bodria: Distretto Sud-Est
Monika Miklaszewska: University of Messina
Natalie S. Uy: Weill Cornell Medicine
Olga Baraldi: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Omar Bjanid: Medical University of Silesia
Pasquale Esposito: University of Genoa
Pasquale Zamboli: AORN San Giuseppe Moscati
Pierluigi Marzuillo: Università degli Studi della Campania “Luigi Vanvitelli”
Pietro A. Canetta: Columbia University Medical Center
Przemyslaw Sikora: Medical University of Lublin
Rik Westland: University of Amsterdam
Russell J. Crew: Columbia University Medical Center
Shumyle Alam: El Paso Children Hospital
Stefano Guarino: Università degli Studi della Campania “Luigi Vanvitelli”
Susanna Negrisolo: University of Padova
Thomas Hays: Columbia University Medical Center
Shrikant Mane: Yale University School of Medicine
Valeria Grandinetti: Spedali Civili and University
Velibor Tasic: Faculty of Medicine
Vladimir J. Lozanovski: Faculty of Medicine
Yasar Caliskan: Saint Louis University
David Goldstein: Columbia University Medical Center
Richard P. Lifton: Rockefeller University
Iuliana Ionita-Laza: Columbia University
Krzysztof Kiryluk: Columbia University Medical Center
Albertien M. van Eerde: University Medical Center Utrecht
Friedhelm Hildebrandt: Harvard Medical School
Simone Sanna-Cherchi: Columbia University Medical Center
Ali G. Gharavi: Columbia University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Congenital anomalies of the kidneys and urinary tract (CAKUT) are developmental disorders that commonly cause pediatric chronic kidney disease and mortality. We examine here rare coding variants in 248 CAKUT trios and 1742 singleton CAKUT cases and compare them to 22,258 controls. Diagnostic and candidate diagnostic variants are detected in 14.1% of cases. We find a significant enrichment of rare damaging variants in constrained genes expressed during kidney development and in genes associated with other developmental disorders, suggesting phenotype expansion. Consistent with these data, 18% of CAKUT patients with diagnostic variants have neurodevelopmental or cardiac phenotypes. We identify 40 candidate genes, including CELSR1, SSBP2, XPO1, NR6A1, and ARID3A. Two are confirmed as CAKUT genes: ARID3A and NR6A1. This study suggests that many yet-unidentified syndromes would be discoverable with larger cohorts and cross-phenotype analysis, leading to clarification of the genetic and phenotypic spectrum of developmental disorders.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62319-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62319-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62319-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().