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Clinical and Molecular Features of POLG-Related Sensory Ataxic Neuropathy with Dysarthria and Ophthalmoparesis

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Abstract

Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is a rare mitochondrial disorder associated with mutations in the POLG gene, which encodes the DNA polymerase gamma catalytic subunit. A few POLG-related SANDO cases have been reported, but the genotype–phenotype correlation remains unclear. Here, we report a patient with SANDO carrying two novel missense variants (c.2543G>C, p.G848A and c.452 T>C, p.L151P) in POLG. We also reviewed previously reported cases to systematically evaluate the clinical and genetic features of POLG-related SANDO. A total of 35 distinct variants in the coding region of POLG were identified in 63 patients with SANDO. The most frequent variant was the p.A467T variant, followed by the p.W748S variant. The clinical spectrum of SANDO is heterogeneous. No clear correlation has been observed between the mutation types and clinical phenotypes. Our findings expand the mutational spectrum of POLG and contribute to clinical management and genetic counseling for POLG-related SANDO.

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Acknowledgments

This article was supported by grants from the National Key R&D Program of China (2018YFC1314700), Shanghai Science and Technology Committee Rising-Star Program (19QA1407900), and the Shanghai Municipal Commission of Health and Family Planning (20184Y0015). We sincerely thank the family members for participating in this study.

Funding

This article was supported by grants from the National Key R&D Program of China (2018YFC1314700), Shanghai Science and Technology Committee Rising-Star Program (19QA1407900), and the Shanghai Municipal Commission of Health and Family Planning (20184Y0015).

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Li-Xi Li: data acquisition, statistical analysis, and writing of the first draft. Li-Ting Jiang: manuscript revision. You-Gui Pan, Xiao-Long Zhang, Li-Zhen Pan, Zhi-Yu Nie, and Yu-Hui Chen: data acquisition. Ling-Jing Jin: study design and manuscript revision.

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Correspondence to Ling-Jing Jin.

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This study was approved by the Ethics Board of Tongji Hospital, Tongji University School of Medicine. The patient and his parents signed written informed consent agreements.

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All authors declare no conflict of interest.

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Li, LX., Jiang, LT., Pan, YG. et al. Clinical and Molecular Features of POLG-Related Sensory Ataxic Neuropathy with Dysarthria and Ophthalmoparesis. J Mol Neurosci 71, 2462–2467 (2021). https://doi.org/10.1007/s12031-021-01831-9

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  • DOI: https://doi.org/10.1007/s12031-021-01831-9

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