IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62319-3.html
   My bibliography  Save this article

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

Author

Listed:
  • Hila Milo Rasouly

    (Columbia University Medical Center
    Columbia University Medical Center)

  • Sarath Babu Krishna Murthy

    (Columbia University Medical Center)

  • Natalie Vena

    (Columbia University Medical Center
    Columbia University Medical Center)

  • Gundula Povysil

    (Columbia University Medical Center
    Waypoint Bio)

  • 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
    Brigham and Women’s Hospital)

  • Jeremiah Martino

    (Columbia University Medical Center
    Pace University)

  • Juntao Ke

    (Columbia University Medical Center)

  • Naama Elefant

    (Columbia University Medical Center
    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
    University of Turin)

  • 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
    Clinical Research Center for Rare Diseases Aldo e Cele Daccò)

  • Victoria Kolupaeva

    (Columbia University Medical Center
    Columbia University Medical Center)

  • Emily E. Groopman

    (Columbia University Medical Center
    Children’s National Hospital)

  • 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
    Icahn School of Medicine at Mount Sinai)

  • 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
    Weill Cornell Medicine)

  • Stacy Piva

    (Columbia University Medical Center)

  • Xueru Mu

    (Columbia University Medical Center)

  • Adele Mittrori

    (Columbia University Medical Center
    University of Bari Aldo Moro)

  • Agnieszka Szmigielska

    (Medical University of Warsaw)

  • Aleksandra Gliwińska

    (Medical University of Silesia)

  • Andrea Ranghino

    (Azienda Ospedaliera Universitaria delle Marche
    Università Politecnica 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
    CMP3VdA)

  • Claudia Izzi

    (University of Brescia and Spedali Civili)

  • Claudio La Scola

    (IRCCS Azienda Ospedaliero-Universitaria di Bologna
    Childhood and Adolescence Rimini. AUSL of Romagna)

  • 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
    Alma Mater Studiorum University of Bologna)

  • Gerald B. Appel

    (Columbia University Medical Center)

  • Gian Marco Ghiggeri

    (Istituto Giannina Gaslini)

  • Gianluigi Zaza

    (University of Calabria)

  • Giovanni Montini

    (Ospedale Maggiore Policlinico
    University of Milan)

  • 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
    AOU Città della Salute e della Scienza Hospital)

  • 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
    AUSL Della Romagna)

  • Omar Bjanid

    (Medical University of Silesia)

  • Pasquale Esposito

    (University of Genoa
    IRCCS Ospedale Policlinico San Martino)

  • 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
    Pediatric Research Institute “IRP Città della Speranza”)

  • 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
    University Medical Center of the Johannes Gutenberg University)

  • Yasar Caliskan

    (Saint Louis University)

  • David Goldstein

    (Columbia University Medical Center
    Actio Biosciences)

  • Richard P. Lifton

    (Rockefeller University)

  • Iuliana Ionita-Laza

    (Columbia University
    Lund 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
    Columbia University Medical Center)

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.

Suggested Citation

  • 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 & Janewi, 2025. "Exome analysis links kidney malformations to developmental disorders and reveals causal genes," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62319-3
    DOI: 10.1038/s41467-025-62319-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62319-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62319-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62319-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.