Further delineation of EBF3-related syndromic neurodevelopmental disorder in twelve Chinese patients

Frontiers in Pediatrics

Pediatrics

Suzhen Xu¹  Xu Li¹  Xuemei Zhao¹  Huijun Wang¹  Jitao Zhu¹  Renchao Liu¹  Qi Ni¹  Sha Yu¹  Qiufang Guo¹  Yao Wang¹  Yanyan Qian¹  Ping Zhang¹  Bingbing Wu¹  Qiong Xu²  Wei Lu³  Sujuan Wang⁴  Shuizhen Zhou⁵  Wenhui Li⁵ 

[1] Center for Molecular Medicine, Pediatrics Research Institute, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;Department of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;Department of Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;Department of Rehabilitation, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;Neurology Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;

关键词: neurodevelopmental disorders (NDDs);    exome sequencing;    EBF3;    novel variants;    copy number variations (CNVs);   

DOI  :  10.3389/fped.2023.1091532

 received in 2022-11-07, accepted in 2023-02-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

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 < 0.01). Our study further expanded the gene mutation spectrum of EBF3-related NDD.

【 授权许可】

Unknown   
© 2023 Zhu, Li, Yu, Lu, Xu, Wang, Qian, Guo, Xu, Wang, Zhang, Zhao, Ni, Liu, Li, Wu, Zhou and Wang.