Genetic Causes for Mitochondrial Disorders May Now Be Rapidly Identified Using New Test

Patients with mitochondrial disorders may be more rapidly diagnosed with a new genetic test developed by researchers at the Wellcome Trust Center for Mitochondrial Research. The new test is described in the study “Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype,” published in The American Journal of Human Genetics.

“The diagnosis of mitochondrial disease is often a complicated and time-consuming process,” Prof. Rob Taylor of the U.K.’s Wellcome Trust Centre for Mitochondrial Research said in a press release. Taylor also leads the NHS Highly Specialised Mitochondrial Diagnostic Laboratory at Newcastle Hospital’s NHS Foundation Trust in England.

“There are over 1,300 potential genes that can lead to disease and, as such, finding the genetic cause is sometimes like looking for a needle in a haystack,” Taylor said.

Mitochondrial disorders may be caused by mutations in either the mitochondrial genome or within the 23 pairs of chromosomes. Given the amount of proteins involved in the mitochondrial respiratory chain — which produces energy for the cell — the clinical presentations associated with each mutation are very heterogeneous. Symptoms include muscle weakness, blindness, diabetes, seizures, learning disabilities, heart and liver failure, and in some cases it can lead to death in early infancy.

The research team had previously reported that mutations in the TMEM126B gene, a previously uncharacterized gene, may lead to problems in energy production in patients’ muscles.

Although there is currently no cure for mitochondrial disorders, understanding which genes are causing the disease in each patient is crucial, not only to adapt preventive measures and plan treatment options, but also when parents of a child with a mitochondrial disorder are planning to have another baby.

“There is sadly no cure for mitochondrial disease, so rapid diagnosis means parents who are wanting to have further children can opt for prenatal testing to ensure future children are healthy and without risk of developing severe disease,” Taylor said. “It provides options for families at risk of an otherwise incurable disease.”

With the new method, the researchers can shorten the diagnosis time from several months to two or three days. In their study, they identified six patients from four distinct families who were affected by mutations in the TMEM126B gene, which codes for a protein involved in the assembly of the mitochondrial complex I.

“Identifying a fault in Complex I, one of the building blocks of mitochondria which is responsible for causing disease combined with our custom gene capture and the latest sequencing technology, means we can screen many more genes to diagnose this debilitating disease,” said Charlotte Alston, the study’s first author.

“It means families can get a rapid diagnosis within days rather than the weeks and months that testing can currently take. For families who are waiting on a genetic diagnosis before trying for another baby, or they may already be expecting their next child, time really is of the essence.”

The routine test is currently available to patients in the U.K. for whom the NHS (National Health Service) funds such highly specialized mitochondrial services.