title: Heterozygous mutation in the X chromosomal NDUFA1 gene in a girl with complex I deficiency.
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.
authors: Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria. h.mayr@salk.at
authors: Johannes A
authors: JA
authors: Mayr
authors: Olaf
authors: O
authors: Bodamer
authors: Tobias B
authors: TB
authors: Haack
authors: Franz A
authors: FA
authors: Zimmermann
authors: Florence
authors: F
authors: Madignier
authors: Holger
authors: H
authors: Prokisch
authors: Christian
authors: C
authors: Rauscher
authors: Johannes
authors: J
authors: Koch
authors: Wolfgang
authors: W
authors: Sperl