Accès ouvert déclaré
2025
article
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 Yin Lim, Anna Jamry-Dziurla, Francesca Lugani, Jun Y Zhang, Maddalena Marasà, Victoria Kolupaeva, Emily 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 Badeński, 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 Krzemień, Isabella Pisani, Jai Radhakrishnan, Katarzyna Zachwieja, Loreto Gesualdo, Luigi Biancone, Davide Meneghesso, Malgorzata Mizerska-Wasiak, Marcin Tkaczyk, Marcin Zaniew, Maria Katarzyna Borszewska-Kornacka, Maria Szczepańska, Marijan Saraga, Maya K. Rao, Monica Bodria, Monika Miklaszewska, Natalie Uy, Olga Baraldi, Omar Bjanid, Pasquale Esposito, Pasquale Zamboli, Pierluigi Marzuillo, Pietro A. Canetta, Przemysław Sikora, Rik Westland, Russell J. Crew, Shumyle Alam, Stefano Guarino, Susanna Negrisolo, Thomas Hays, Shrikant Mane, Valeria Grandinetti, Velibor Tasić, Vladimir J. Lozanovski, Yaşar Çalışkan, David Dowling Samuel Goldstein, Richard P. Lifton, Iuliana Ionita-laza, Krzysztof Kiryluk, Albertien M. van Eerde, Friedhelm Hildebrandt, Simone Sanna-Cherchi, Ali G. Gharavi, Groep van Eerde, Child Health, Genetica Klinische Genetica, Cancer
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Le résumé fourni par la source
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.
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Les sujets associés
Renal and related cancersRenal cell carcinoma treatmentPancreatic function and diabetes