title: Specific diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in dried blood spots by a polymerase chain reaction (PCR) assay detecting a point-mutation (G985) in the MCAD gene.
abstract: The discovery of a point-mutation, adenine-to-guanine, at position 985 in the gene coding for MCAD (G985), gave the basis for an easy and specific polymerase chain reaction test. We tested the specificity of such a PCR based assay and detected correctly G985 and A985 in sequence verified cDNA clones. We showed that the G985 mutation is present in genomic DNA from 48 of 50 patients with confirmed MCAD deficiency, originating from various European countries, Australia and the USA. On the basis of this high frequency of the G985 mutation among patients, we improved and optimized the assay with respect to reliability and convenience for routine diagnostic and screening purposes. As little as 2 microliters blood from filter-paper blood-spots (Guthrie spots) is sufficient for the test.
authors.affiliation: University Department of Clinical Chemistry, Aarhus Kommunehospital, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Gregersen
authors.forename: A I
authors.initials: AI
authors.lastname: Blakemore
authors.forename: V
authors.initials: V
authors.lastname: Winter
authors.forename: B
authors.initials: B
authors.lastname: Andresen
authors.forename: S
authors.initials: S
authors.lastname: Kølvraa
authors.forename: L
authors.initials: L
authors.lastname: Bolund
authors.forename: D
authors.initials: D
authors.lastname: Curtis
authors.forename: P C
authors.initials: PC
authors.lastname: Engel
mesh_terms: D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D000225:Adenine; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D006147:Guanine; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D006147:Guanine; D004247:DNA; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase; D000225:Adenine