Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene

Mol Genet Metab. 2014 Nov;113(3):207-12. doi: 10.1016/j.ymgme.2014.06.004. Epub 2014 Jun 30.


Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of developmental delay, sensorineural hearing loss, epilepsy, agenesis of the corpus callosum, failure to thrive, and stroke-like episodes. Sequencing of the mitochondrial genome identified a novel de novo, heteroplasmic mutation in the mitochondrial DNA (mtDNA) encoded ATP6 gene (m.8969G>A, p.S148N). Whole exome sequencing did not identify mutations or variants in PUS1 or YARS2 or any known nuclear genes that could affect mitochondrial function and explain this phenotype. Studies of fibroblasts derived from the patient revealed a decrease in oligomycin-sensitive respiration, a finding which is consistent with a complex V defect. Thus, this mutation in MT-ATP6 may represent the first mtDNA point mutation associated with the MLASA phenotype.

Keywords: ATP6; Lactic acidosis; MLASA; Mitochondria; Mitochondrial myopathy.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / diagnosis*
  • Acidosis, Lactic / genetics
  • Amino Acid Sequence
  • Anemia, Sideroblastic / diagnosis*
  • Anemia, Sideroblastic / genetics
  • Cell Respiration
  • Cells, Cultured
  • Child
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Genetic Association Studies
  • Humans
  • Male
  • Mitochondrial Myopathies / diagnosis*
  • Mitochondrial Myopathies / genetics
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Molecular Sequence Data
  • Point Mutation


  • DNA, Mitochondrial
  • MT-ATP6 protein, human
  • Mitochondrial Proton-Translocating ATPases