Mitochondrial diseases: expanding the diagnosis in the era of genetic testing

Abstract

Mitochondrial diseases are clinically and genetically heterogeneous. These diseases were initially described a little over three decades ago. Limited diagnostic tools created disease descriptions based on clinical, biochemical analytes, neuroimaging, and muscle biopsy findings. This diagnostic mechanism continued to evolve detection of inherited oxidative phosphorylation disorders and expanded discovery of mitochondrial physiology over the next two decades. Limited genetic testing hampered the definitive diagnostic identification and breadth of diseases. Over the last decade, the development and incorporation of massive parallel sequencing has identified approximately 300 genes involved in mitochondrial disease. Gene testing has enlarged our understanding of how genetic defects lead to cellular dysfunction and disease. These findings have expanded the understanding of how mechanisms of mitochondrial physiology can induce dysfunction and disease, but the complete collection of disease-causing gene variants remains incomplete. This article reviews the developments in disease gene discovery and the incorporation of gene findings with mitochondrial physiology. This understanding is critical to the development of targeted therapies.

The efficacy of coenzyme Q10treatment in alleviating the symptoms of primary coenzyme Q10deficiency: a systematic review

“…Thus, the mutation frequency observed for a given COQ gene is likely influenced by the role it plays in CoQ biosynthesis and its tissue expression pattern. With increasing affordability and accessibility of genome or exome sequencing [60], more and more PCoQD patients are being reported, and a more accurate picture of PCoQD patients’ frequency should soon emerge.…”

Utilization of Human Samples for Assessment of Mitochondrial Bioenergetics: Gold Standards, Limitations, and Future Perspectives

“…While testing of muscle biopsies was considered the gold standard, before the genomics era, to measure mitochondrial bioenergetic function and diagnosis of primary mitochondrial disease [79], alternative methods would be preferentially useful for diagnosis and research when genetic screening is not enough for categorization of the deficiency [80]. Identifying suitable alternatives to muscle biopsies and systemic biomarkers of mitochondrial function has become a major research focus.…”

Excessively Enlarged Mitochondria in the Kidneys of Diabetic Nephropathy

“…The regulation machinery of mitochondrial dynamics has been identified in yeast and Drosophila models, and homolog proteins have also been found in mammalian models [ 17 , 18 ]. These include the fusion regulation factors, mitofusin 1 and 2 (Mfn1/2) and optic atrophy 1 (Opa1), and the fission regulation factors, dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) [ 18 ].…”