npj Genomic Medicine (Mar 2024)
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
- Jil D. Stegmann,
- Jeshurun C. Kalanithy,
- Gabriel C. Dworschak,
- Nina Ishorst,
- Enrico Mingardo,
- Filipa M. Lopes,
- Yee Mang Ho,
- Phillip Grote,
- Tobias T. Lindenberg,
- Öznur Yilmaz,
- Khadija Channab,
- Steve Seltzsam,
- Shirlee Shril,
- Friedhelm Hildebrandt,
- Felix Boschann,
- André Heinen,
- Angad Jolly,
- Katherine Myers,
- Kim McBride,
- Mir Reza Bekheirnia,
- Nasim Bekheirnia,
- Marcello Scala,
- Manuela Morleo,
- Vincenzo Nigro,
- Annalaura Torella,
- TUDP consortium,
- Michele Pinelli,
- Valeria Capra,
- Andrea Accogli,
- Silvia Maitz,
- Alice Spano,
- Rory J. Olson,
- Eric W. Klee,
- Brendan C. Lanpher,
- Se Song Jang,
- Jong-Hee Chae,
- Philipp Steinbauer,
- Dietmar Rieder,
- Andreas R. Janecke,
- Julia Vodopiutz,
- Ida Vogel,
- Jenny Blechingberg,
- Jennifer L. Cohen,
- Kacie Riley,
- Victoria Klee,
- Laurence E. Walsh,
- Matthias Begemann,
- Miriam Elbracht,
- Thomas Eggermann,
- Arzu Stoppe,
- Kyra Stuurman,
- Marjon van Slegtenhorst,
- Tahsin Stefan Barakat,
- Maureen S. Mulhern,
- Tristan T. Sands,
- Cheryl Cytrynbaum,
- Rosanna Weksberg,
- Federica Isidori,
- Tommaso Pippucci,
- Giulia Severi,
- Francesca Montanari,
- Michael C. Kruer,
- Somayeh Bakhtiari,
- Hossein Darvish,
- Heiko Reutter,
- Gregor Hagelueken,
- Matthias Geyer,
- Adrian S. Woolf,
- Jennifer E. Posey,
- James R. Lupski,
- Benjamin Odermatt,
- Alina C. Hilger
Affiliations
- Jil D. Stegmann
- Institute of Human Genetics, Medical Faculty, University of Bonn
- Jeshurun C. Kalanithy
- Institute of Human Genetics, Medical Faculty, University of Bonn
- Gabriel C. Dworschak
- Institute of Human Genetics, Medical Faculty, University of Bonn
- Nina Ishorst
- Institute of Human Genetics, Medical Faculty, University of Bonn
- Enrico Mingardo
- Institute of Anatomy and Cell Biology, Medical Faculty, University of Bonn
- Filipa M. Lopes
- Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester
- Yee Mang Ho
- Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester
- Phillip Grote
- Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy
- Tobias T. Lindenberg
- Institute of Neuroanatomy, Medical Faculty, University of Bonn
- Öznur Yilmaz
- Institute of Neuroanatomy, Medical Faculty, University of Bonn
- Khadija Channab
- Institute of Anatomy and Cell Biology, Medical Faculty, University of Bonn
- Steve Seltzsam
- Division of Nephrology, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School
- Shirlee Shril
- Division of Nephrology, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School
- Friedhelm Hildebrandt
- Division of Nephrology, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School
- Felix Boschann
- Institute of Medical Genetics and Human Genetics, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
- André Heinen
- Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
- Angad Jolly
- Department of Molecular & Human Genetics, Baylor College of Medicine
- Katherine Myers
- Center for Cardiovascular Research, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University
- Kim McBride
- Center for Cardiovascular Research, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University
- Mir Reza Bekheirnia
- Department of Molecular & Human Genetics, Baylor College of Medicine
- Nasim Bekheirnia
- Department of Pediatrics, Renal Service, Texas Children’s Hospital
- Marcello Scala
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa
- Manuela Morleo
- Medical Genetics, Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’
- Vincenzo Nigro
- Medical Genetics, Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’
- Annalaura Torella
- Medical Genetics, Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’
- TUDP consortium
- Michele Pinelli
- Telethon Institute of Genetics and Medicine
- Valeria Capra
- Genomics and Clinical Genetics, IRCCS Gaslini
- Andrea Accogli
- Division of Medical Genetics, Department of Specialized Medicine, McGill University
- Silvia Maitz
- Medical Genetics Service, Oncology Department of Southern Switzerland, Ente Ospedaliero Cantonale
- Alice Spano
- MBBM Foundation
- Rory J. Olson
- Center for Individualized Medicine, Mayo Clinic
- Eric W. Klee
- Center for Individualized Medicine, Mayo Clinic
- Brendan C. Lanpher
- Center for Individualized Medicine, Mayo Clinic
- Se Song Jang
- Department of Pediatrics, Seoul National University College of Medicine
- Jong-Hee Chae
- Department of Pediatrics, Seoul National University College of Medicine
- Philipp Steinbauer
- Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University of Vienna
- Dietmar Rieder
- Division of Bioinformatics, Medical University of Innsbruck
- Andreas R. Janecke
- Department of Pediatrics I, Medical University of Innsbruck
- Julia Vodopiutz
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, Comprehensive Center for Pediatrics, Medical University of Vienna
- Ida Vogel
- Department of Clinical Medicine, Aarhus University
- Jenny Blechingberg
- Department of Clinical Genetics, Aarhus University Hospital
- Jennifer L. Cohen
- Division of Medical Genetics, Department of Pediatrics, Duke University
- Kacie Riley
- Department of Pediatrics, Duke University Medical Center
- Victoria Klee
- Pediatric Neurology, Riley Hospital for Children Indiana University Health
- Laurence E. Walsh
- Pediatric Neurology, Riley Hospital for Children Indiana University Health
- Matthias Begemann
- Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University
- Miriam Elbracht
- Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University
- Thomas Eggermann
- Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University
- Arzu Stoppe
- Division of Neuropediatrics and Social Pediatrics, Department of Pediatrics, Medical Faculty, RWTH Aachen University
- Kyra Stuurman
- Department of Clinical Genetics, Erasmus MC University Medical Center
- Marjon van Slegtenhorst
- Department of Clinical Genetics, Erasmus MC University Medical Center
- Tahsin Stefan Barakat
- Department of Clinical Genetics, Erasmus MC University Medical Center
- Maureen S. Mulhern
- Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons
- Tristan T. Sands
- Division of Child Neurology, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Morgan Stanley Children’s Hospital
- Cheryl Cytrynbaum
- Department of Genetic Counselling, The Hospital for Sick Children
- Rosanna Weksberg
- Department of Molecular Genetics, University of Toronto
- Federica Isidori
- U.O. Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Tommaso Pippucci
- U.O. Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Giulia Severi
- U.O. Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Francesca Montanari
- U.O. Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna
- Michael C. Kruer
- Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children’s Hospital
- Somayeh Bakhtiari
- Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow Neurological Institute, Phoenix Children’s Hospital
- Hossein Darvish
- Neuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences
- Heiko Reutter
- Institute of Human Genetics, Medical Faculty, University of Bonn
- Gregor Hagelueken
- Institute of Structural Biology, University Hospital Bonn, University of Bonn
- Matthias Geyer
- Institute of Structural Biology, University Hospital Bonn, University of Bonn
- Adrian S. Woolf
- Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester
- Jennifer E. Posey
- Department of Molecular & Human Genetics, Baylor College of Medicine
- James R. Lupski
- Department of Molecular & Human Genetics, Baylor College of Medicine
- Benjamin Odermatt
- Institute of Anatomy and Cell Biology, Medical Faculty, University of Bonn
- Alina C. Hilger
- Department of Pediatric and Adolescent Medicine, Friedrich-Alexander University of Erlangen-Nürnberg
- DOI
- https://doi.org/10.1038/s41525-024-00398-9
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 12
Abstract
Abstract CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.
