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Sulaiman et al. J Transl Genet Genom 2020;4:159-87 Journal of Translational
DOI: 10.20517/jtgg.2020.27 Genetics and Genomics

Review Open Access

Advancement in the diagnosis of mitochondrial
diseases

Siti Aishah Sulaiman, Zamzureena Mohd Rani, Fara Zela Mohd Radin, Nor Azian Abdul Murad

UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras 56000, Kuala Lumpur, Malaysia.
Correspondence to: Dr. Nor Azian Abdul Murad, UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latif, Cheras
56000, Kuala Lumpur, Malaysia. E-mail: nor_azian@ppukm.ukm.edu.my

How to cite this article: Sulaiman SA, Mohd Rani Z, Radin FZM, Abdul Murad NA. Advancement in the diagnosis of mitochondrial
diseases. J Transl Genet Genom 2020;4:159-87. http://dx.doi.org/10.20517/jtgg.2020.27

Received: 20 Mar 2020 First Decision: 13 Apr 2020 Revised: 28 Apr 2020 Accepted: 18 May 2020 Published: 18 Jun 2020
Science Editor: Andrea L. Gropman Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

Abstract
Mitochondrial diseases are multi-systemic, heterogeneous groups of diseases that are associated with various
neuromuscular problems, cardiovascular disorders, metabolic syndrome, cancer, and obesity. Mitochondrial
diseases are due to mutations in mitochondrial DNA or nuclear DNA that can affect the assembly of the
mitochondrial components and mitochondrial function. Typically, mitochondrial diseases can be inherited through
an autosomal dominant, autosomal recessive or X-linked pattern of inheritance. To date, there are more than 100
mitochondrial diseases identified. However, clinical phenotype heterogeneity is a huge problem for the diagnosis
of mitochondrial diseases, as patients with the same mutations exhibit different clinical symptoms. Also, the
heteroplasmy/homoplasmy conditions complicate the diagnosis process. Here, in this review, we discuss these
challenges and problems in mitochondrial disease diagnosis, focusing on the mutational profile of both primary and
secondary mitochondrial diseases. We also review the utilization of next-generation technology and multi-omics
strategy to improve the diagnosis. The discussion addresses the current evidence of those applications and the
challenges that need some improvement for better diagnosis yield.

Keywords: Genomics, next-generation sequencing, mtDNA, mitochondrial diseases

INTRODUCTION
Mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA) or nuclear DNA
(nDNA) that encodes mitochondrial components. Mitochondrial diseases are complex diseases involving
multiple organ systems, and the symptoms include deafness, blindness, dementia, movement disorders,
[1]
cardiovascular diseases, and renal dysfunction . Neurological and neuromuscular syndromes are the most
[1,2]
common symptoms of mitochondrial diseases . In addition, cardiovascular diseases, endocrine disorders,
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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