| Autor: |
Jitao Zhu, Wenhui Li, Sha Yu, Wei Lu, Qiong Xu, Sujuan Wang, Yanyan Qian, Qiufang Guo, Suzhen Xu, Yao Wang, Ping Zhang, Xuemei Zhao, Qi Ni, Renchao Liu, Xu Li, Bingbing Wu, Shuizhen Zhou, Huijun Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Frontiers in Pediatrics, Vol 11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2296-2360 |
| DOI: |
10.3389/fped.2023.1091532 |
| Popis: |
Neurodevelopmental disorders (NDDs) have heterogeneity in both clinical characteristics and genetic factors. EBF3 is a recently discovered gene associated with a syndromic form of NDDs characterized by hypotonia, ataxia and facial features. In this study, we report twelve unrelated individuals with EBF3 variants using next-generation sequencing. Five missense variants (four novel variants and one known variant) and seven copy number variations (CNVs) of EBF3 gene were identified. All of these patients exhibited developmental delay/intellectual disability. Ataxia was observed in 33% (6/9) of the patients, and abnormal muscle tone was observed in 55% (6/11) of the patients. Aberrant MRI reports were noted in 64% (7/11) of the patients. Four novel missense variants were all located in the DNA-binding domain. The pathogenicity of these variants was validated by in vitro experiments. We found that the subcellular protein localization of the R152C and F211L mutants was changed, and the distribution pattern of the R163G mutant was changed from even to granular. Luciferase assay results showed that the four EBF3 mutants' transcriptional activities were all significantly decreased (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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