Whole-Genome Sequencing Helpful When a Mitochondrial Disorder Is Suspected

By Reuters Staff

November 10, 2021

NEW YORK (Reuters Health) - Whole-genome sequencing (WGS) can shorten the "diagnostic odyssey" for patients with suspected mitochondrial disorders, report researchers in the United Kingdom.

Mitochondrial disorders affect about one in 5,000 people and are among the most common cause of inherited metabolic disease, yet are tough for clinicians to diagnose. Current genetic testing protocols fail to diagnose about 40% of patients.

Researchers with the University of Cambridge set out to see whether WGS could be used to define the molecular basis of suspected mitochondrial disorders in patients evaluated in mainstream secondary care as well as tertiary centers in the U.K. National Health Service (NHS).

Participants included 319 families with suspected mitochondrial disease recruited through the 100,000 Genomes Project, which was set up to introduce and embed genomic testing in the NHS, discover new disease genes and make genetic diagnosis available for more patients.

WGS, performed in a total of 345 people (median age, 25 years), led to a definite or probable genetic diagnosis for 98 families (31%). Standard genetic tests failed to reach these diagnoses. WGS also led to six possible diagnoses (2% of the 98 families).

Non-mitochondrial disorders (62.5%) were more common than mitochondrial disorders and had features resembling mitochondrial diseases, the researchers found. These non-mitochondrial disorders included developmental disorders with intellectual disability, severe epileptic conditions and metabolic disorders, as well as heart and neurological diseases.

"These patients were referred because of a suspected mitochondrial disease and the conventional diagnostic tests are specifically for mitochondrial diseases. Unless you consider these other possibilities, you won't diagnose them. Whole genome sequencing isn't restricted by that bias," study researcher Dr. Patrick Chinnery said in a news release.

"We recommend that whole genome sequencing should be offered early and before invasive tests such as a muscle biopsy," he said.

"A definitive genetic diagnosis can really help patients and their families, giving them access to tailored information about prognosis and treatment, genetic counseling and reproductive options including preimplantation genetic diagnosis or prenatal diagnosis," added study researcher Dr. Katherine Schon, also with University of Cambridge.

The study did not have commercial funding.

SOURCE: https://bit.ly/3ENDKBk The BMJ, online November 2, 2021.