LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR tomographic, and biochemical study

Mitochondrion. 2017 Nov:37:55-61. doi: 10.1016/j.mito.2017.07.001. Epub 2017 Jul 8.

Abstract

LYRM7 is involved in the last steps of mitochondrial complex III assembly where it acts as a chaperone for the Rieske iron‑sulfur (Fe-S) protein in the mitochondrial matrix. Using exome sequencing, we identified homozygosity for a splice site destroying 4 base pair deletion in LYRM7 in a child with recurrent lactic acidotic crises and distinct early-onset leukencephalopathy. Sanger sequencing showed variant segregation in similarly affected family members. Functional analyses revealed a reduced amount of the Rieske Fe-S protein, which was restored after re-expression of LYRM7. Our data provide further evidence for the importance of LYRM7 for mitochondrial function and emphasize the importance of whole exome sequencing in the diagnosis of rare mitochondrial diseases.

Keywords: Complex III; Encephalopathy; LYRM7; Lactic acidosis; Mitochondriopathy; Whole exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Acidosis, Lactic / complications
  • Acidosis, Lactic / genetics
  • Acidosis, Lactic / pathology
  • Child, Preschool
  • Electron Transport Complex III / analysis
  • Electron Transport Complex III / deficiency*
  • Female
  • Humans
  • Infant
  • Leukoencephalopathies / complications
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / pathology
  • Mitochondria / enzymology*
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism*
  • Sequence Deletion

Substances

  • LYRM7 protein, human
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Rieske iron-sulfur protein
  • Electron Transport Complex III