Heterozygous mutation in the X chromosomal NDUFA1 gene in a girl with complex I deficiency

Mol Genet Metab. 2011 Aug;103(4):358-61. doi: 10.1016/j.ymgme.2011.04.010. Epub 2011 May 5.

Abstract

Respiratory chain enzymes consist of multiple subunits encoded either by the mitochondrial or by the nuclear genome. Recently the first X-chromosomal mutations in complex I deficient males have been described. Heterozygous female carriers did not seem to be affected. Here, we describe a girl initially presenting with mild muscular hypotonia, a moderate lactic acidosis and an increased beta-hydroxybutyrate/acetoacetate ratio. Biochemical investigations of a muscle biopsy revealed a deficiency in the amount and activity of complex I. Mutation screening of all structural subunits of complex I identified a heterozygous mutation c.94G>C, p.Gly32Arg in the X-chromosomal NDUFA1 gene. Analysis of the cDNA showed that 72% of the expressed mRNA was mutated in the muscle biopsy sample. Investigation of the X-inactivation pattern demonstrated that 74% of the paternally inherited allele was active in the muscle. This is the first report of an X-chromosomally inherited respiratory chain defect in a heterozygous female.

Publication types

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

MeSH terms

  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics
  • Female
  • Genes, X-Linked*
  • Genetic Diseases, X-Linked / genetics*
  • Heterozygote*
  • Humans
  • Infant
  • Mutation*
  • NADH Dehydrogenase / genetics*
  • RNA, Messenger / metabolism

Substances

  • RNA, Messenger
  • NADH Dehydrogenase
  • Electron Transport Complex I
  • NDUFA1 protein, human