Complete mtDNA sequencing reveals mutations m.9185T>C and m.13513G>A in three patients with Leigh syndrome

Abstract

The most common mitochondrial disorder in children is Leigh syndrome, which is a progressive and genetically heterogeneous neurodegenerative disorder caused by mutations in nuclear genes or mitochondrial DNA (mtDNA). In the present study, a novel and robust method of complete mtDNA sequencing, which allows amplification of the whole mitochondrial genome, was tested. Complete mtDNA sequencing was performed in a cohort of patients with suspected mitochondrial mutations. Patients from Latvia and Lithuania (n = 92 and n = 57, respectively) referred by clinical geneticists were included. The de novo point mutations m.9185T>C and m.13513G>A, respectively, were detected in two patients with lactic acidosis and neurodegenerative lesions. In one patient with neurodegenerative lesions, the mutation m.9185T>C was identified. These mutations are associated with Leigh syndrome. The present data suggest that full-length mtDNA sequencing is recommended as a supplement to nuclear gene testing and enzymatic assays to enhance mitochondrial disease diagnostics.

Keywords:

• Leigh syndrome
• mitochondrial DNA
• brain MRI

Disclosure statement

D.P., E.J., J.S., L.P. and I.I. have granted a European patent for a kit for detecting mutation or polymorphism in the human mitochondrial DNA (EP3091083 (A1), dated 9 November 2016). The remaining authors report no conflicts of interest.

Additional information

Funding

The study was supported by European Regional Development Fund (ERDF) grant 2010/0223/2DP/2.1.1.1.0/10/APIA/VIAA/025 ‘New tests for the diagnosis of inherited neuromuscular diseases’, and ERDF Grant 2014/0021/2DP/2.1.1.1.0/14/APIA/VIAA/058 ‘Development of novel in vitro tests for diagnostics and prognostics of individualized therapies of tumors and mitochondrial disease treatment’. The study was also supported by the Taiwan-Latvian-Lithuanian Collaboration Project ‘Functional model for the mitochondrial disease evaluation and biomarker development’.