Deep sequencing discovery of causal mtDNA mutations in a patient with unspecific neurological disease

In this study we have sequenced the mitochondrial genome of a girl with an unspecific neurological disorder and her mother. The later, while neurologically unaffected, suffers from a myopathy without clear cause. We were able to detect two non-synonymous mutations in the MT-ATP6 gene, which we propose are strong candidates for causative agents. 9017C as the main candidate present at high heteroplasmy frequency in the patient (83,2%) and moderate in the mother (45,4%) while it has a low frequency in the general population. It might act alone or in conjunction with 9010A as an accessory mutation. Evolutionary analysis showed that both mutations were located in a critical position in the F0 a subunit, from F0-F1 ATPase. Functional studies showed that carriers of those mutations in comparison to an unaffected individual (father) presented a decrease in the basal and ATP-dependent oxygen consumption rate and a decrease in the maximum respiration rate.
Source: Mitochondrion - Category: Biochemistry Source Type: research