Publication Date
3-1-2024
Journal
npj Genomic Medicine
DOI
10.1038/s41525-024-00398-9
PMID
38429302
PMCID
PMC10907620
PubMedCentral® Posted Date
3-1-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Development, Neurodevelopmental disorders, Kidney diseases, Genetic testing, Urogenital diseases
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.
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