PUBLICATION
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
- Authors
- Stegmann, J.D., Kalanithy, J.C., Dworschak, G.C., Ishorst, N., Mingardo, E., Lopes, F.M., Ho, Y.M., Grote, P., Lindenberg, T.T., Yilmaz, Ö., Channab, K., Seltzsam, S., Shril, S., Hildebrandt, F., Boschann, F., Heinen, A., Jolly, A., Myers, K., McBride, K., Bekheirnia, M.R., Bekheirnia, N., Scala, M., Morleo, M., Nigro, V., Torella, A., TUDP consortium, Pinelli, M., Capra, V., Accogli, A., Maitz, S., Spano, A., Olson, R.J., Klee, E.W., Lanpher, B.C., Jang, S.S., Chae, J.H., Steinbauer, P., Rieder, D., Janecke, A.R., Vodopiutz, J., Vogel, I., Blechingberg, J., Cohen, J.L., Riley, K., Klee, V., Walsh, L.E., Begemann, M., Elbracht, M., Eggermann, T., Stoppe, A., Stuurman, K., van Slegtenhorst, M., Barakat, T.S., Mulhern, M.S., Sands, T.T., Cytrynbaum, C., Weksberg, R., Isidori, F., Pippucci, T., Severi, G., Montanari, F., Kruer, M.C., Bakhtiari, S., Darvish, H., Reutter, H., Hagelueken, G., Geyer, M., Woolf, A.S., Posey, J.E., Lupski, J.R., Odermatt, B., Hilger, A.C.
- ID
- ZDB-PUB-240303-6
- Date
- 2024
- Source
- NPJ genomic medicine 9: 1818 (Journal)
- Registered Authors
- Barakat, Stefan, Hildebrandt, Friedhelm, Ishorst, Nina, Klee, Eric W., Odermatt, Benjamin
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 38429302 Full text @ NPJ Genom Med
Citation
Stegmann, J.D., Kalanithy, J.C., Dworschak, G.C., Ishorst, N., Mingardo, E., Lopes, F.M., Ho, Y.M., Grote, P., Lindenberg, T.T., Yilmaz, Ö., Channab, K., Seltzsam, S., Shril, S., Hildebrandt, F., Boschann, F., Heinen, A., Jolly, A., Myers, K., McBride, K., Bekheirnia, M.R., Bekheirnia, N., Scala, M., Morleo, M., Nigro, V., Torella, A., TUDP consortium, Pinelli, M., Capra, V., Accogli, A., Maitz, S., Spano, A., Olson, R.J., Klee, E.W., Lanpher, B.C., Jang, S.S., Chae, J.H., Steinbauer, P., Rieder, D., Janecke, A.R., Vodopiutz, J., Vogel, I., Blechingberg, J., Cohen, J.L., Riley, K., Klee, V., Walsh, L.E., Begemann, M., Elbracht, M., Eggermann, T., Stoppe, A., Stuurman, K., van Slegtenhorst, M., Barakat, T.S., Mulhern, M.S., Sands, T.T., Cytrynbaum, C., Weksberg, R., Isidori, F., Pippucci, T., Severi, G., Montanari, F., Kruer, M.C., Bakhtiari, S., Darvish, H., Reutter, H., Hagelueken, G., Geyer, M., Woolf, A.S., Posey, J.E., Lupski, J.R., Odermatt, B., Hilger, A.C. (2024) Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies. NPJ genomic medicine. 9:1818.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping