Mainstreaming proteomics into rare disease diagnostics

Abstract

Mitochondrial diseases are a group of highly heterogeneous disorders caused by mutations in over 350 known genes. Reported genomic diagnostic yields for mitochondrial disorders are in the range of 40–60%. A factor contributing to a lack of molecular diagnosis is the availability of functional tests to demonstrate variant pathogenicity in a timely and cost-effective manner. The gold-standard and National Association of Testing Authorities (NATA)/Royal College of Pathologists of Australasia (RCPA) accredited functional test measures the enzyme activities of mitochondrial respiratory chain complexes I–IV, however this test is not specific as defects in hundreds of genes can lead to an abnormal result.