Rapid Genetic Test Developed for an Often Fatal Mitochondrial Disease

Researchers have discovered disease-causing inherited mutations in the TMEM126B gene and developed a test providing rapid diagnosis of related mitochondrial disorders. Defects in TMEM126B cause problems with energy generation in muscles, and can lead to muscular weakness, blindness, fatal heart failure, liver failure, learning disability, diabetes, and seizures. There is currently no cure and affected children often die in early infancy.

A team of medics and scientists at Wellcome Trust Centre for Mitochondrial Research, Newcastle University (Newcastle, Tyne & Wear, UK), together with international collaborators identified the mutations and used next generation sequencing (NGS) to develop the test, which provides a result within 2-3 days. Their research confirmed the identity of a mutation in TMEM126B that causes mitochondrial disease affecting Complex I, one of five complexes involved in energy production. TMEM126B normally makes a protein necessary for complex I assembly.


First author Charlotte Alston, PhD student, described the technique, which has already identified 6 patients from 4 families affected by this form of mitochondrial disease: “Identifying a fault in Complex I [...] combined with our custom gene capture and the latest sequencing technology means we can screen many more genes to diagnose this debilitating disease. 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.”

Senior author Professor Rob Taylor said: “The diagnosis of mitochondrial disease is often a complicated and time consuming process. 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.”

For a family with one child affected with this type of mitochondrial disease, there is a 25% chance of each further child being affected. Professor Taylor added: “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. It provides options for families at risk of an otherwise incurable disease.”

The study, by Alston CL et al, was published July 7, 2016, in the American Journal of Human Genetics.

Related Links:
Newcastle University
Wellcome Trust Centre for Mitochondrial Research