title: Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy.
abstract: Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.
authors.affiliation: Department of Medical Genetics, Vrije Universiteit, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: De Meirleir
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: C
authors.initials: C
authors.lastname: Benelli
authors.forename: G
authors.initials: G
authors.lastname: Ponsot
authors.forename: I
authors.initials: I
authors.lastname: Desguerre
authors.forename: C
authors.initials: C
authors.lastname: Marsac
authors.forename: D
authors.initials: D
authors.lastname: Rodriguez
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: F
authors.initials: F
authors.lastname: Poggi
authors.forename: I
authors.initials: I
authors.lastname: Liebaers
mesh_terms: D001483:Base Sequence; D002493:Central Nervous System Diseases / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease; D012326:RNA Splicing
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit