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

Johannes A. Mayr, Olaf Bodamer, Tobias B. Haack, Franz A. Zimmermann, Florence Madignier, Holger Prokisch, Christian Rauscher, Johannes Koch, Wolfgang Sperl

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.94. G > 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.

Original languageEnglish (US)
Pages (from-to)358-361
Number of pages4
JournalMolecular Genetics and Metabolism
Issue number4
StatePublished - Aug 2011


  • Complex I
  • Mitochondrial energy metabolism
  • NDUFA1
  • Respiratory chain
  • X-inactivation

ASJC Scopus subject areas

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


Dive into the research topics of 'Heterozygous mutation in the X chromosomal NDUFA1 gene in a girl with complex I deficiency'. Together they form a unique fingerprint.

Cite this