Advancing the diagnosis of mitochondrial diseases with genomic sequencing

Abstract

Mitochondrial diseases are the most common metabolic disease, caused by pathogenic variants in both nuclear and mitochondrial genomes. The molecular diagnosis can be challenging, sometimes taking years and requiring multiple invasive and risky diagnostic techniques. Genome sequencing (GS) is an emerging technology that allows the analysis of nuclear and mitochondrial genomes simultaneously. However, the interpretation of data can be complex, and the use of this technology in mitochondrial diseases is limited. This PhD thesis explores the diagnostic utility of GS by investigating retrospective and prospective cohorts of patients with suspected (but molecularly undiagnosed) mitochondrial dis..