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01-10-2021 | Original Article

Novel biallelic mutations in POLG gene: large deletion and missense variant associated with PEO

Authors: Yan Lin, Jixiang Du, Wei Wang, Hong Ren, Dandan Zhao, Fuchen Liu, Pengfei Lin, Kunqian Ji, Yuying Zhao, Chuanzhu Yan

Published in: Neurological Sciences | Issue 10/2021

Abstract

Background

Mitochondrial disorders are clinically heterogeneous diseases associated with impaired oxidative phosphorylation (OXPHOS) activity. POLG, which encodes the DNA polymerase-γ (Polγ) catalytic subunit, is the most commonly mutated nuclear gene associated with mitochondrial disorders.

Methods

We carried out whole-exome sequencing (WES) to identify the gene associated with progressive external ophthalmoplegia (PEO). We then performed histopathological analyses, assessed mitochondrial biology, and executed functional studies to evaluate the potential pathogenicity of the identified genetic mutations.

Results

Novel biallelic POLG mutations, including a large deletion mutation (exons 7–21) and a missense variant c.1796C>T (p.Thr599Ile) were detected in the proband. Histopathological analysis of a biopsied muscle sample from this patient revealed the presence of approximately 20% COX-negative fibers. Bioinformatics analyses confirmed that the detected mutations were pathogenic. Furthermore, levels of mitochondrial complex I, II, and IV subunit protein expressions were found to be decreased in the proband, and marked impairment of mitochondrial respiration was evident in cells harboring these mutations.

Conclusion

This study expands the spectrum of known POLG variants associated with PEO and advances current understanding regarding the structural and functional impacts of these mutations.

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Title: Novel biallelic mutations in POLG gene: large deletion and missense variant associated with PEO
Authors: Yan Lin
Jixiang Du
Wei Wang
Hong Ren
Dandan Zhao
Fuchen Liu
Pengfei Lin
Kunqian Ji
Yuying Zhao
Chuanzhu Yan
Publication date: 01-10-2021
Publisher: Springer International Publishing
Published in: Neurological Sciences / Issue 10/2021
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05380-2

At a glance: The STEP trials

Springer Medicine

Novel biallelic mutations in POLG gene: large deletion and missense variant associated with PEO

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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