title: X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.
abstract: Three female patients are described with pyruvate dehydrogenase (PDH) deficiency as a result of mutation in the X-linked gene for the E1 alpha subunit of the complex. Two of these patients illustrate typical presentations of PDH E1 alpha deficiency, with severe neurological dysfunction, degenerative changes and developmental anomalies in the brain, together with variable lactic acidosis. The third patient extends the known spectrum of the condition to include mild to moderate mental retardation and seizures in an adult. All three patients have the same mutation in the PDH E1 alpha gene. This mutation, a C-to-T substitution in a CpG dinucleotide in amino acid codon 302 (designated R302C), results in the replacement of arginine by cysteine at this position. The mildly affected adult was the mother of one of the other patient, making this the first described instance of mother-to-daughter transmission of a mutation causing PDH E1 alpha deficiency. The genetic basis of the variable expression of X-linked PDH E1 alpha deficiency in heterozygous females is discussed.
authors.affiliation: Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Melbourne, Australia.
authors.forename: H H
authors.initials: HH
authors.lastname: Dahl
authors.forename: L L
authors.initials: LL
authors.lastname: Hansen
authors.forename: R M
authors.initials: RM
authors.lastname: Brown
authors.forename: D M
authors.initials: DM
authors.lastname: Danks
authors.forename: J G
authors.initials: JG
authors.lastname: Rogers
authors.forename: G K
authors.initials: GK
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics* / Q000378:metabolism; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D014960:X Chromosome
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D030481:Pyruvate Dehydrogenase (Lipoamide)