title: First prenatal diagnosis of defects in the HsPDX1 gene encoding protein X, an additional lipoyl-containing subunit of the human pyruvate dehydrogenase complex.
abstract: We have previously reported a genetic study of a neonatal lactic acidosis linked to a pyruvate dehydrogenase complex deficiency due to the absence of the protein X subunit. This rare autosomal recessive disorder is associated with specific deletions in this polypeptide which is encoded by the HsPDX1 gene, located on chromosome 11p1.3. The pathology of the patient was considered to arise from a large homozygous deletion (78del85) found at the 5' end of the HsPDX1 coding sequence. Her heterozygous mother underwent prenatal diagnosis during a subsequent pregnancy. Chorionic villus samples were used for three independent studies: (1) normal levels of the protein X component of the PDH complex were detected by immunoblotting; (2) RT-PCR analysis showed no deletion at the 5' end of the cDNA but the presence of a distinct heterozygous deletion (965del59) at its 3' end inherited from the father; (3) haplotype analysis revealed the presence of the father's mutated allele and the mother's normal allele. It was concluded that the fetus was heterozygous for this separate 3' deletion, so, it was likely to be not affected. This study permitted us to characterize more precisely the genetic abnormalities of the HsPDX1 cDNA occurring in each family's member.
authors.affiliation: Centre de Recherches Thérapeutiques en Ophtalmologie (CERTO), Faculté de Médecine Necker, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Rouillac
authors.forename: B
authors.initials: B
authors.lastname: Aral
authors.forename: F
authors.initials: F
authors.lastname: Fouque
authors.forename: D
authors.initials: D
authors.lastname: Marchant
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: Y
authors.initials: Y
authors.lastname: Dumez
authors.forename: G
authors.initials: G
authors.lastname: Lindsay
authors.forename: M
authors.initials: M
authors.lastname: Abitbol
authors.forename: J L
authors.initials: JL
authors.lastname: Dufier
authors.forename: C
authors.initials: C
authors.lastname: Marsac
authors.forename: C
authors.initials: C
authors.lastname: Benelli
mesh_terms: D015153:Blotting, Western; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations / Q000175:diagnosis*; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007888:Leigh Disease / Q000175:diagnosis*; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D011768:Pyruvate Dehydrogenase Complex; D012313:RNA