The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia

Mitochondrial DNA. 2015 Apr;26(2):208-12. doi: 10.3109/19401736.2014.905860. Epub 2014 Apr 8.

Abstract

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

Keywords: Cortical deafness; NADH dehydrogenase subunit 3 gene; mitochondrial disorders.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Agnosia / diagnosis
  • Agnosia / genetics*
  • DNA, Mitochondrial / chemistry*
  • Electron Transport Complex I / genetics*
  • Genes, Mitochondrial
  • Genotyping Techniques
  • Humans
  • Leigh Disease / diagnosis
  • Leigh Disease / genetics*
  • MELAS Syndrome / diagnosis
  • MELAS Syndrome / genetics*
  • Magnetic Resonance Imaging
  • Point Mutation*

Substances

  • DNA, Mitochondrial
  • Electron Transport Complex I
  • MT-ND3 protein, human