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

Lindsay C. Burrage, Sha Tang, Jing Wang, Taraka R. Donti, Magdalena Walkiewicz, J. Michael Luchak, Li Chieh Chen, Eric S. Schmitt, Zhiyv Niu, Rodrigo Erana, Jill V. Hunter, Brett H. Graham, Lee Jun Wong, Fernando Scaglia

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-212
Number of pages6
JournalMolecular genetics and metabolism
Volume113
Issue number3
DOIs
StatePublished - Nov 1 2014

Keywords

  • ATP6
  • Lactic acidosis
  • MLASA
  • Mitochondria
  • Mitochondrial myopathy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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    Burrage, L. C., Tang, S., Wang, J., Donti, T. R., Walkiewicz, M., Luchak, J. M., Chen, L. C., Schmitt, E. S., Niu, Z., Erana, R., Hunter, J. V., Graham, B. H., Wong, L. J., & Scaglia, F. (2014). 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. Molecular genetics and metabolism, 113(3), 207-212. https://doi.org/10.1016/j.ymgme.2014.06.004