| Title | Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Stegmann, 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 Authors | TUDP consortium |
| Journal | NPJ Genom Med |
| Volume | 9 |
| Issue | 1 |
| Pagination | 18 |
| Date Published | 2024 Mar 01 |
| ISSN | 2056-7944 |
| 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. |
| DOI | 10.1038/s41525-024-00398-9 |
| Alternate Journal | NPJ Genom Med |
| PubMed ID | 38429302 |
| PubMed Central ID | PMC10907620 |
| Grant List | MR/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 |