Next-generation sequencing for mitochondrial disorders

Abstract

A great deal of our understanding of mitochondrial function has come from studies of inherited mitochondrial diseases, but still majority of the patients lack molecular diagnosis. Furthermore, effective treatments for mitochondrial disorders do not exist. Development of therapies has been complicated by the fact that the diseases are extremely heterogeneous, and collecting large enough cohorts of similarly affected individuals to assess new therapies properly has been difficult. Next-generation sequencing technologies have in the last few years been shown to be an effective method for the genetic diagnosis of inherited mitochondrial diseases. Here we review the strategies and findings from studies applying next-generation sequencing methods for the genetic diagnosis of mitochondrial disorders. Detailed knowledge of molecular causes also enables collection of homogenous cohorts of patients for therapy trials, and therefore boosts development of intervention.

Keywords: diagnosis; exome; mitochondria; mitochondrial disease; next-generation sequencing.

Figure 1

A workflow for the molecular diagnosis of patients with genetic disease using exome sequencing. Shown in rectangles are considerations to be made when applying exome sequencing for mitochondrial disorders at each of the steps.