Study Recommends mtDNA Sequencing in Patients with Suspected Mitochondrial Disease

Researchers discovered a new mutation in the mitochondrial genome with disease-causing potential when screening potential patients for new mitochondrial mutations.

The study, “A novel MTTT mutation m.15933G > A revealed in analysis of mitochondrial DNA in patients with suspected mitochondrial disease,” highlighted the importance of thoroughly screening the mitochondrial DNA of patients with suspected mitochondrial disease who do not have known mutations. The work was published in the journal BMC Medical Genetics.

When doctors suspect that someone suffers from mitochondrial disease, there is a battery of genetic tests to unearth if the person carries mutations known to cause disease. But in a proportion of patients, these tests do not find any faults.

And while the tests are quick and straightforward, a full sequencing of the coding regions of the mitochondrial genome is not. Large deletions in genes are also not detected by standard sequencing and require specific methods for discovery.

Researchers at the University of Oulu in Finland recruited 66 patients with suspected mitochondrial disease based on observed symptoms. Using sequencing methods that could detect both small changes and large deletions, the research team discovered three homoplastic point mutations that had not been reported earlier. Homoplasmy is a term used to explain that all mitochondria in a sample have an identical DNA sequence.

Since each cell holds thousands of mitochondria that divide independently of the cell, many mutations are only found in a proportion of the mitochondria, a feature called heteroplasmy. This is particularly true for newer mutations.

Analyses of the homoplastic gene variants suggested that one of them was directly causing disease. The team also discovered three rare variants that might contribute to disease.

In addition, the team detected 47 point mutations that caused a change in the amino acid sequence of the protein. Using computer-generated algorithms, researchers predicted that five of them caused mitochondrial disease. Earlier studies have shown that three of them are inherited together with other known mitochondrial gene variants.

Two patients carried multiple deletions. One of the patients did not have any other disease-causing mutations, so the deletions were the likely cause of his disease.

“Sequencing of the mtDNA coding region is recommended for patients presenting with symptoms of a mitochondrial disorder but lacking the common disease-causing mutations in mtDNA,” the researchers concluded.