Exploring mito-nuclear genetic factors in Leber's hereditary optic neuropathy

insights from comprehensive profiling of unique cases

Authors

  • Prakash Chermakani Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India; Department of Molecular Biology, Aravind Medical Research Foundation - Affiliated to Alagappa University, Karaikudi, Tamil Nadu, India https://orcid.org/0000-0002-3792-3808
  • Poigaialwar Gowri Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India; Department of Molecular Biology, Aravind Medical Research Foundation - Affiliated to Alagappa University, Karaikudi, Tamil Nadu, India https://orcid.org/0000-0002-8882-7146
  • Shanmugam Mahesh Kumar Neuro Ophthalmology Clinic, Aravind Eye Hospital, Madurai, Tamil Nadu, India https://orcid.org/0000-0002-3628-7352
  • Periasamy Sundaresan Department of Molecular Genetics, Aravind Medical Research Foundation, 1, Anna Nagar, Madurai -625020, Tamil Nadu, India. Phone: +91-452-435 6100 (Extn: 423), E-mail: sundar@aravind.org https://orcid.org/0000-0002-0599-8653

DOI:

https://doi.org/10.17179/excli2023-6297

Keywords:

mitochondrial complex I disorder, retinoganglion degeneration, mito-nuclear genetic factors, arLHON, optic atrophy and vision loss

Abstract

Leber's hereditary optic neuropathy (LHON) is a mitochondrial complex I disorder and causes inexorable painless vision loss. Recent studies from India reported that a significant proportion of LHON patients lack primary mitochondrial DNA mutations, suggesting that alternative genetic factors contribute to disease development. Therefore, this study investigated the genetic profile of LHON-affected individuals in order to understand the role of mito-nuclear genetic factors in LHON. A total of thirty probands displaying symptoms consistent with LHON have undergone whole mitochondrial and whole exome sequencing. Interestingly, whole mtDNA sequencing revealed primary mtDNA mutations in 30 % of the probands (n=9), secondary mtDNA mutations in 40 % of the probands (n=12) and no mitochondrial changes in 30 % of individuals (n=9). Further, WES analysis determined pathogenic mutations in 11 different nuclear genes, especially in cases with secondary mtDNA mutations (n=6) or no mtDNA mutations (n=6). These findings provide valuable insight into LHON genetic predisposition, particularly in cases lacking primary mtDNA mutations.

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Published

2023-10-09

How to Cite

Chermakani, P., Gowri, P., Mahesh Kumar, S., & Sundaresan, P. (2023). Exploring mito-nuclear genetic factors in Leber’s hereditary optic neuropathy: insights from comprehensive profiling of unique cases. EXCLI Journal, 22, 1077–1091. https://doi.org/10.17179/excli2023-6297

Issue

Vol. 22 (2023)

Section

Original articles

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Copyright (c) 2023 Prakash Chermakani, Poigaialwar Gowri, Shanmugam Mahesh Kumar, Periasamy Sundaresan

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