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.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 language | English (US) |
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Pages (from-to) | 358-361 |
Number of pages | 4 |
Journal | Molecular Genetics and Metabolism |
Volume | 103 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2011 |
Keywords
- Complex I
- Mitochondrial energy metabolism
- NDUFA1
- Respiratory chain
- X-inactivation
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
- Endocrinology
- Endocrinology, Diabetes and Metabolism