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

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

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).

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