Abstract
CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.
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Acknowledgements
The authors are grateful to the patient and his family for their participation in this study. This research project was supported by the Henan Children’s Hospital. The authors would also like to express their gratitude to all individuals who assisted throughout this project.
Funding
National Natural Science Foundation of China (81701125); National Population Health Data Center Project (sub-project: SJPT-03-01) Henan Medical Education Research Project (Wjlx2022148).
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Kai-Li Xu, Li Wang, Dai-Qi Mei, and Liu-Jiong Gao provided clinical data. Xiao-Man Zhang, Jing-Hui Kong, Geng Dong, Shi-Jie Dong, Zhi-Xiao Yang, Shu-Jing Xu and Wei-Yue Gu analyzed data. Xiao-Man Zhang, Shu-Ying Luo, Yao-Dong Zhang, and Shi-Yue Mei drafted and edited the manuscript. All authors contributed to editing.
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Zhang, XM., Xu, KL., Kong, JH. et al. Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review. J Hum Genet 69, 197–203 (2024). https://doi.org/10.1038/s10038-024-01230-z
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DOI: https://doi.org/10.1038/s10038-024-01230-z
