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

TitleBi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.
Publication TypeJournal Article
Year of Publication2024
AuthorsStegmann, JD, Kalanithy, JC, Dworschak, GC, Ishorst, N, Mingardo, E, Lopes, FM, Ho, YMang, 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, MReza, 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, SSong, Chae, J-H, 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, TStefan, 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, AC
Corporate AuthorsTUDP consortium
JournalNPJ Genom Med
Date Published2024 Mar 01

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.

Alternate JournalNPJ Genom Med
PubMed ID38429302
PubMed Central IDPMC10907620
Grant ListMR/T016809/1 / MRC_ / Medical Research Council / United Kingdom
UM1 HG006542 / HG / NHGRI NIH HHS / United States
K08 HG008986 / HG / NHGRI NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States
U01 HG011758 / HG / NHGRI NIH HHS / United States
R35 NS105078 / NS / NINDS NIH HHS / United States
R01 DK076683 / DK / NIDDK NIH HHS / United States