In vivo modeling of novel de novo WDR44 variants associated with corpus callosal dysgenesis
- Title
- In vivo modeling of novel de novo WDR44 variants associated with corpus callosal dysgenesis
- Authors
- BAEK, SEUNG TAE; 소기헌; 김동휘
- Date Issued
- 2021-05-20
- Publisher
- 한국뇌신경과학회
- Abstract
- Clinical whole-exome sequencing (WES) has facilitated identifying novel
candidates for rare neurodevelopmental disorders, especially for undiagnosed
cases. Here we describe two patients presenting corpus callosal (CC)
dysgenesis. WES revealed de novo missense mutations in WDR44 predicted
to be possibly damaging in silico. To functionally validate variants’ pathogenicity,
we ectopically overexpressed the variants in developing mouse
embryos. Overexpression of both variants in neurons resulted in migration
defect and morphological abnormality during early neurodevelopment. Ectopic
expression of variants in the embryonic brain led to postnatal CC
anomalies as well as reduced ipsilateral and contralateral axon branching
mimicking pathologies seen in the patients. Our in vivo modeling characterized
the effects of novel WDR44 variants, and this may provide opportunities
for understanding the pathologies of associated neurodevelopmental
disorders.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/109778
- Article Type
- Conference
- Citation
- KSBNS 2021, 2021-05-20
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