Please use this identifier to cite or link to this item:
https://doi.org/10.1126/sciadv.aax9852
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dc.title | PRDM15 loss of function links NOTCH and WNT/PCP signaling to patterning defects in holoprosencephaly | |
dc.contributor.author | Mzoughi, S. | |
dc.contributor.author | Di Tullio, F. | |
dc.contributor.author | Low, D.H.P. | |
dc.contributor.author | Motofeanu, C.-M. | |
dc.contributor.author | Ong, S.L.M. | |
dc.contributor.author | Wollmann, H. | |
dc.contributor.author | Wun, C.M. | |
dc.contributor.author | Kruszka, P. | |
dc.contributor.author | Muenke, M. | |
dc.contributor.author | Hildebrandt, F. | |
dc.contributor.author | Dunn, N.R. | |
dc.contributor.author | Messerschmidt, D.M. | |
dc.contributor.author | Guccione, E. | |
dc.date.accessioned | 2021-08-24T02:38:17Z | |
dc.date.available | 2021-08-24T02:38:17Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Mzoughi, S., Di Tullio, F., Low, D.H.P., Motofeanu, C.-M., Ong, S.L.M., Wollmann, H., Wun, C.M., Kruszka, P., Muenke, M., Hildebrandt, F., Dunn, N.R., Messerschmidt, D.M., Guccione, E. (2020). PRDM15 loss of function links NOTCH and WNT/PCP signaling to patterning defects in holoprosencephaly. Science Advances 6 (2) : eaax9852. ScholarBank@NUS Repository. https://doi.org/10.1126/sciadv.aax9852 | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/198952 | |
dc.description.abstract | Holoprosencephaly (HPE) is a congenital forebrain defect often associated with embryonic lethality and lifelong disabilities. Currently, therapeutic and diagnostic options are limited by lack of knowledge of potential disease-causing mutations. We have identified a new mutation in the PRDM15 gene (C844Y) associated with a syndromic form of HPE in multiple families. We demonstrate that C844Y is a loss-of-function mutation impairing PRDM15 transcriptional activity. Genetic deletion of murine Prdm15 causes anterior/posterior (A/P) patterning defects and recapitulates the brain malformations observed in patients. Mechanistically, PRDM15 regulates the transcription of key effectors of the NOTCH and WNT/PCP pathways to preserve early midline structures in the developing embryo. Analysis of a large cohort of patients with HPE revealed potentially damaging mutations in several regulators of both pathways. Our findings uncover an unexpected link between NOTCH and WNT/PCP signaling and A/P patterning and set the stage for the identification of new HPE candidate genes. Copyright @ 2020 The Authors, some rights reserved; | |
dc.publisher | American Association for the Advancement of Science | |
dc.rights | Attribution-NonCommercial 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | Scopus OA2020 | |
dc.type | Article | |
dc.contributor.department | BIOCHEMISTRY | |
dc.description.doi | 10.1126/sciadv.aax9852 | |
dc.description.sourcetitle | Science Advances | |
dc.description.volume | 6 | |
dc.description.issue | 2 | |
dc.description.page | eaax9852 | |
Appears in Collections: | Staff Publications Elements |
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