Mitochondrial genome sequencing: A valuable addition to whole exome sequencing for the molecular diagnosis of mitochondrial disorders

There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders.The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006–2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively.The study cohort included 18 patients (age range: 18 months–50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n = 11), SURF1 mutations (n = 4) and POLG1(n = 3). Axonal neuropathy was noted in 12 patients (sensori-motor:n = 4; sensory:n = 4; motor:n = 4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy.A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder.