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Observation of novel COX20 mutations related to autosomal recessive axonal neuropathy and static encephalopathy

Abstract

Cytochrome c oxidase 20 (COX20)/FAM36A encodes a conserved protein that is important for the assembly of COX, complex IV of the mitochondrial respiratory chain. A homozygous mutation (p.Thr52Pro) in COX20 gene has been previously described to cause muscle hypotonia and ataxia. In this study, we describe two patients from a non-consanguineous family exhibiting autosomal recessive sensory-dominant axonal neuropathy and static encephalopathy. The whole-exome sequencing analysis revealed that both patients harbored compound heterozygous mutations (p.Lys14Arg and p.Trp74Cys) of COX20 gene. The pathogenicity of the variants was further supported by morphological alternations of mitochondria observed in sural nerve and decreased COX20 protein level of peripheral blood leucocytes derived from the patients. In conclusion, COX20 might be considered as a candidate gene for the complex inherited disease. This observation broadens the clinical and genetic spectrum of COX20-related disease. However, due to the limitation of a single-family study, additional cases and studies are definitely needed to further confirm the association.

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Acknowledgements

We sincerely thank the participants for their cooperation and unwavering dedication to this study and the anonymous reviewers whose help improved this manuscript.

Funding

This work was supported by the following grants: The Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 81601093); The Young Scientists Fund of the First Affiliated Hospital of Zhengzhou University (2015, Director: Hongliang Xu).

Author information

XHL and JT wrote the paper. XHL, JT and LYJ conceived the idea and evaluated the patients. XHL and JT analyzed the genetic results. XHL and LS performed the sural nerve biopsy. XHL, JT, YYH and DXB evaluated the pathological findings. CX, WSY and XHL performed the Western blotting. LYJ supervised the diagnosis and treatment. All authors approved the final version of the manuscript.

Correspondence to Yajun Lian.

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Conflict of interest

All authors declare that they have no conflict of interests.

Informed consent

Written informed consent was obtained from the patients and/or their guardians prior to sample collection and open sural nerve biopsy.

Ethical approval

This study was approved by the ethics committee of the Zhengzhou University First Hospital and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Xu, H., Ji, T., Lian, Y. et al. Observation of novel COX20 mutations related to autosomal recessive axonal neuropathy and static encephalopathy. Hum Genet 138, 749–756 (2019). https://doi.org/10.1007/s00439-019-02026-4

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