Exome sequencing enhances the ability to identify potential nuclear gene mutations in patients with biochemically defined defects affecting multiple mitochondrial respiratory chain complexes. Additional study is required in independent patient populations to determine the utility of this approach in comparison with traditional diagnostic methods.

Inherited ataxias are difficult to diagnose genetically. Pyle et al. use whole-exome sequencing to provide a likely molecular diagnosis in 14 of 22 families with ataxia. The approach reveals de novo mutations, broadens the phenotype of other disease genes, and is equally effective in young and older-onset patients.