Clinical and molecular study in a long-surviving patient with MLASA syndrome due to novel PUS1 mutations

Neurogenetics. 2016 Jan;17(1):65-70. doi: 10.1007/s10048-015-0465-x. Epub 2015 Nov 10.

Abstract

Myopathy-lactic acidosis-sideroblastic anemia (MLASA) syndrome is a rare autosomal recessive disease. We studied a 43-year-old female presenting since childhood with mild cognitive impairment and sideroblastic anemia. She later developed hepatopathy, cardiomyopathy, and insulin-dependent diabetes. Muscle weakness appeared in adolescence and, at age 43, she was unable to walk. Two novel different mutations in the PUS1 gene were identified: c.487delA (p.I163Lfs*4) and c.884 G>A (p.R295Q). Quantitative analysis of DNA from skeletal muscle biopsies showed a significant increase in mitochondrial DNA (mtDNA) content in the patient compared to controls. Clinical and molecular findings of this patient widen the genotype-phenotype spectrum in MLASA syndrome.

Keywords: MLASA; Mitochondrial biogenesis; PUS1; mtDNA copy number.

Publication types

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

MeSH terms

  • Adult
  • DNA Mutational Analysis
  • Female
  • Humans
  • Hydro-Lyases / chemistry
  • Hydro-Lyases / genetics*
  • MELAS Syndrome / genetics*
  • MELAS Syndrome / pathology*
  • Magnetic Resonance Imaging
  • Mitochondrial Myopathies / genetics
  • Mitochondrial Myopathies / pathology
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Survivors
  • Syndrome

Substances

  • Hydro-Lyases
  • pseudouridylate synthetase

Supplementary concepts

  • Myopathy with lactic acidosis and sideroblastic anemia