학술논문
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
Document Type
article
Author
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
Source
npj Genomic Medicine, Vol 9, Iss 1, Pp 1-12 (2024)
Subject
Language
English
ISSN
2056-7944
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.