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Compound heterozygous variants of THG1L result in autosomal recessive cerebellar ataxia

Journal of Human Genetics volume 68, pages 843–848 (2023)Cite this article

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Abstract

tRNA-histidine guanyltransferase 1-like protein (THG1L), located in the mitochondria, plays a crucial role in the tRNA maturation process. Dysfunction of THG1L results in abnormal mitochondrial tRNA modification and neurodevelopmental disorders. To date, few studies have focused on THG1L-related cerebellar ataxia. Whole-exome sequencing revealed compound heterozygous variants NM_017872.5: [c.224A > G]; [c.369-8T > G] in THG1L in a 6-year-old boy with moderate cerebellar ataxia. The variant c.224A > G was demonstrated to downregulate its RNA and protein expression, and c.369-8 T > G resulted in a 7 bp insertion before exon 3. Our case expanded the gene variation and clinical spectrum of THG1L-related cerebellar ataxia.

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Acknowledgements

We thank Mr. Zuozhen Yang from CipherGene LLC for his support in manuscript review and editing. This work was supported by the Joint Construction Project of Medical Science and Technology in Henan Province (LHGJ20200452).

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Authors and Affiliations

  1. Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China

    Rui Han, Manman Chu, Junling Wang, Mengyue Wang, Yichao Ma, Tianming Jia & Xiaoli Zhang

  2. Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, Henan, China

    Jinshuang Gao

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  1. Rui Han
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Contributions

RH, MC: conceptualization, methodology, experiments, paper writing; JG, JW: data analysis, variant interpretation; MW, YM: sample collection, phenotypic description, patient follow-up; TJ, XZ: funding, supervision, manuscript reviewing, and editing. All authors read and approved the final version of the manuscript.

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Correspondence to Xiaoli Zhang.

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Han, R., Chu, M., Gao, J. et al. Compound heterozygous variants of THG1L result in autosomal recessive cerebellar ataxia. J Hum Genet 68, 843–848 (2023). https://doi.org/10.1038/s10038-023-01192-8

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