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Novel compound heterozygous mutation and phenotype in the tetratricopeptide repeat-like domain of the GEMIN5 gene in two Chinese families

Journal of Human Genetics volume 68, pages 789–792 (2023)Cite this article

Subjects

Abstract

Background

GEMIN5 is an RNA-binding protein that regulates multiple molecular functions, including splicing, localisation, translation, and mRNA stability. GEMIN5 mutations present a syndrome centred on cerebellar dysplasia, including motor dysfunction, developmental delay, cerebellar atrophy, and hypotonia.

Cases

We report three patients from two families with novel compound heterozygous mutations in the tetratricopeptide repeat-like domain of the GEMIN5 gene who presented with motor dysfunction, developmental delay, and ataxia syndrome.

Novel variants were identified: c.2551_c.2552delCT (Leu851Glufs*30) and c.2911 C > G (Gln971Glu) in Family 1, and c.3287 T > C (Leu1096Pro) and c.2882 G > C (Trp961 Ser) in Family 2, which were inherited from their parents. Moreover, infantile spasms syndrome(ISs) was diagnosed in the family.

Conclusion

We report the first case of ISs caused by GEMIN5 gene mutations. Our cases expand on GEMIN5 variants and neurological phenotypes, reinforcing the crucial impact of tetratricopeptide repeat-like domain variants in the GEMIN5 gene.

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Acknowledgements

We want to thank the patients who contributed samples to the study. We acknowledge the support from STI 2030-Major Projects and the Zhejiang Provincial Natural Science Foundation of China.

Funding

This study was funded by STI 2030-Major Projects under Grant No. 2021ZD0201700 and the Zhejiang Provincial Natural Science Foundation of China under Grant No. LGF19H090020.

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Authors and Affiliations

  1. Department of Neurology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310003, China

    Xin Zhang, Lu Xu, Yilong Wang, Guoxia Sheng, Feng Gao & Zhefeng Yuan

  2. Department of Rehabilitation, Xi’an TCM Hospital of Encephalopathy, Xi’an, 710032, China

    Yanzhao Guo

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  1. Xin Zhang
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  2. Yanzhao Guo
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Correspondence to Yanzhao Guo or Zhefeng Yuan.

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Ethics approval and consent to participate

The studies involving human participants were reviewed and Approved by the Ethics Committee of Children’s Hospital, Zhejiang University School of Medicine (2021-IRB-161). The participants’ legal guardians/next of kin provided written informed consent to participate in this study.

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Zhang, X., Guo, Y., Xu, L. et al. Novel compound heterozygous mutation and phenotype in the tetratricopeptide repeat-like domain of the GEMIN5 gene in two Chinese families. J Hum Genet 68, 789–792 (2023). https://doi.org/10.1038/s10038-023-01184-8

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