A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion

Neuromuscul Disord. 2009 Feb;19(2):147-50. doi: 10.1016/j.nmd.2008.11.014. Epub 2009 Jan 12.

Abstract

This report describes two brothers, both deceased in infancy, with severe depletion of mitochondrial DNA (mtDNA) in muscle tissue. Both had feeding difficulties, failure to thrive, severe muscular hypotonia and lactic acidosis. One of the boys developed a renal proximal tubulopathy. A novel homozygous c.686 G-->T missense mutation in the RRM2B gene, encoding the p53-inducible ribonucleotide reductase subunit (p53R2), was identified. This is the third report on mutations in RRM2B associated with severe mtDNA depletion, which further highlights the importance of de novo synthesis of deoxyribonucleotides (dNTPs) for mtDNA maintenance.

Publication types

  • Case Reports

MeSH terms

  • Acidosis, Lactic / genetics
  • Acidosis, Lactic / metabolism
  • Acidosis, Lactic / physiopathology
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / physiopathology
  • Cell Cycle Proteins / genetics*
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Deoxyribonucleotides / biosynthesis
  • Down-Regulation
  • Fatal Outcome
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Homozygote
  • Humans
  • Infant
  • Male
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / physiopathology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / metabolism
  • Muscle Hypotonia / physiopathology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Diseases / genetics*
  • Muscular Diseases / metabolism
  • Muscular Diseases / physiopathology
  • Mutation, Missense / genetics*
  • Ribonucleotide Reductases / genetics*
  • Sequence Homology, Amino Acid

Substances

  • Cell Cycle Proteins
  • DNA, Mitochondrial
  • Deoxyribonucleotides
  • Genetic Markers
  • RRM2B protein, human
  • Ribonucleotide Reductases