Mitochondrial genome analysis increases the diagnostic yield of genetic testing
Sep 23, 2022

However, unique characteristics mean that it isn’t always considered for standard genome testing – even when it should be

Mitochondrial DNA (mtDNA) disorders are recognized as one of the most common causes of inherited metabolic disorders. mtDNA disorders can come with a range of symptoms such as fatigue, exercise intolerance, hearing loss, seizures, strokes, heart failure, diabetes, and kidney failure. There are approximately 120 mitochondrial disorders described affecting 1 in 5000 individuals worldwide.

Mitochondria, located in almost all cells in the body, are responsible for the cell’s energy production and other metabolic functions. In order to function normally, the mitochondria rely on enzymes and proteins coded for by genes in both the nuclear DNA in addition to genes located in the mitochondria itself (mtDNA genome). The mtDNA genome itself is small, circular, and built of 16,569 DNA base pairs which make up the 37 genes that encode for different proteins, transfer RNA, and the ribosomal RNA. This is different from the nuclear mitochondrial DNA which consists of several billion base pairs packaged in 100s of genes and resides within the 46 nuclear chromosomes.

Offspring inherit mitochondria (therefore the mtDNA genome) from their mother – an important point as any mtDNA genome mutations are also passed on

As mtDNA is critically important for many pathways producing energy within the mitochondria, a mutation in one of the genes can lead to a mitochondrial disorder, which will involve the inability to produce sufficient energy for organs like the muscle, brain, and kidney. Symptoms of mtDNA disorders can be multisystemic or limited to a single organ, difficult to differentiate from other more common diseases, and vary greatly, even among family members. This variability in symptoms makes managing such a disorder difficult to diagnose and manage.

The mtDNA genome is maternally inherited and thus a mtDNA mutation will be passed on to every child born from a mother who carries an mtDNA genome mutation. This is different from the nuclear mtDNA where a mutation can be inherited from either parent or both.

Last modified: September 23, 2022