Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies

Stegmann JD, Kalanithy JC, Dworschak GC, Ishorst N, Mingardo E, Lopes FM, Ho YM, Grote P, Lindenberg TT, Yilmaz Ö, Channab K, Seltzsam S, Shril S, Hildebrandt F, Boschann F, Heinen A, Jolly A, Myers K, McBride K, Bekheirnia MR, Bekheirnia N, Scala M, Morleo M, Nigro V, Torella A, Pinelli M, Capra V, Accogli A, Maitz S, Spano A, Olson RJ, Klee EW, Lanpher BC, Jang SS, Chae JH, Steinbauer P, Rieder D, Janecke AR, Vodopiutz J, Vogel I, Blechingberg J, Cohen JL, Riley K, Klee V, Walsh LE, Begemann M, Elbracht M, Eggermann T, Stoppe A, Stuurman K, van Slegtenhorst M, Barakat TS, Mulhern MS, Sands TT, Cytrynbaum C, Weksberg R, Isidori F, Pippucci T, Severi G, Montanari F, Kruer MC, Bakhtiari S, Darvish H, Reutter H, Hagelueken G, Geyer M, Woolf AS, Posey JE, Lupski JR, Odermatt B, Hilger A (2024)


Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 9

Article Number: 18

Journal Issue: 1

DOI: 10.1038/s41525-024-00398-9

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.

Authors with CRIS profile

Involved external institutions

Medizinische Universität Wien AT Austria (AT) Aarhus University DK Denmark (DK) Aarhus University Hospital / Aarhus Universitetshospital DK Denmark (DK) Duke University US United States (USA) (US) Duke University Medical Center US United States (USA) (US) Riley Hospital for Children at Indiana University Health US United States (USA) (US) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE) Erasmus University Medical Center (MC) NL Netherlands (NL) Columbia University Irving Medical Center (CUIMC) US United States (USA) (US) The Hospital for Sick Children (SickKids) CA Canada (CA) University of Toronto CA Canada (CA) Ospedaliero Universitaria di Bologna Policlinico S.Orsola-Malpighi IT Italy (IT) Barrow Neurological Institute US United States (USA) (US) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Baylor College of Medicine US United States (USA) (US) Texas Children's Hospital US United States (USA) (US) University of Genova / Università degli Studi di Genova IT Italy (IT) Università degli studi della Campania Luigi Vanvitelli IT Italy (IT) Telethon Institute of Genetics and Medicine (TIGEM) IT Italy (IT) Istituto Giannina Gaslini IT Italy (IT) McGill University CA Canada (CA) Ente Ospedaliero Cantonale CH Switzerland (CH) Fondazione Monza E Brianza Per Il Bambino E La Sua Mamma Onlus (MBBM) IT Italy (IT) Mayo Clinic US United States (USA) (US) University of Manchester GB United Kingdom (GB) Georg-Speyer-Haus DE Germany (DE) Seoul National University (SNU) / 서울대학교 KR Korea, Republic of (KR) Medizinische Universität Innsbruck AT Austria (AT) Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Ohio State University US United States (USA) (US) Golestan University of Medical Sciences (GoUMS) IR Iran, Islamic Republic of (IR)

How to cite

APA:

Stegmann, J.D., Kalanithy, J.C., Dworschak, G.C., Ishorst, N., Mingardo, E., Lopes, F.M.,... Hilger, A. (2024). Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies. npj Genomic Medicine, 9(1). https://doi.org/10.1038/s41525-024-00398-9

MLA:

Stegmann, Jil D., et al. "Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies." npj Genomic Medicine 9.1 (2024).

BibTeX: Download