Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.
Jil D StegmannJeshurun C KalanithyGabriel C DworschakNina IshorstEnrico MingardoFilipa M LopesYee Mang HoPhillip GroteTobias T LindenbergÖznur YilmazKhadija ChannabSteve SeltzsamShirlee ShrilFriedhelm HildebrandtFelix BoschannAndré HeinenAngad JollyKatherine MyersKim McBrideMir Reza BekheirniaNasim BekheirniaMarcello ScalaManuela MorleoVincenzo NigroAnnalaura Torellanull nullMichele PinelliValeria CapraAndrea AccogliSilvia MaitzAlice SpanoRory J OlsonEric W KleeBrendan C LanpherSe Song JangJong-Hee ChaePhilipp SteinbauerDietmar RiederAndreas R JaneckeJulia VodopiutzIda VogelJenny BlechingbergJennifer L CohenKacie RileyVictoria KleeLaurence E WalshMatthias BegemannMiriam ElbrachtEggermann ThomasArzu StoppeKyra StuurmanMarjon van SlegtenhorstTahsin Stefan BarakatMaureen S MulhernTristan T SandsCheryl CytrynbaumRosanna WeksbergFederica IsidoriTommaso PippucciGiulia SeveriFrancesca MontanariMichael C KruerSomayeh BakhtiariHossein DarvishHeiko Martin ReutterGregor HageluekenMatthias GeyerAdrian S WoolfJennifer E PoseyJames R. LupskiBenjamin OdermattAlina C HilgerPublished in: NPJ genomic medicine (2024)
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.