title: Assessment of the prevalence of the 985A>G MCAD mutation in the French-Canadian population using allele-specific PCR.
abstract: Inherited deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is a severe, sometimes fatal disorder. A single mutation in the MCAD gene, 985A>G, is involved in approximately 90% of cases. To evaluate the relevance of implementing a systematic population-based screening program in the province of Quebec using a biochemical test, we measured the prevalence of this mutation in a set of anonymous newborn samples from the Quebec City area, a region where the majority of its inhabitants are French-Canadians. An allele-specific polymerase chain reaction assay was designed and used to detect the mutation in 7143 DNA samples obtained from consecutive anonymous newborns. Pools of eight DNA samples were genotyped in parallel for the same mutation to validate this pooling strategy. The allelic frequency of the MCAD 985A>G mutation was found to be 0.71% and the carrier frequency 1:71 (95% confidence interval 1:55 to 1:98). This estimate predicts a homozygous frequency of 1:19,837. Ninety-nine heterozygous carriers and one homozygous individual were identified out of 7143 samples. There was 100% concordance between the individual and pooled analyses, and the pooling strategy reduced the total genotyping costs by approximately 70%. The carrier frequency estimated for this population is similar to other northwestern European populations and would support implementation of systematic newborn screening (such as tandem mass spectrometry screening) for this disease. Pooling DNA samples followed by genotyping appears to be cost-effective for estimating prevalence of rare mutations.
authors.affiliation: Unité de Recherche en Génétique Humaine et Moléculaire, Centre de Recherche de l'Hôpital St-François d'Assise du Centre Hospitalier Universitaire de Québec, Québec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Giroux
authors.forename: A
authors.initials: A
authors.lastname: Dubé-Linteau
authors.forename: G
authors.initials: G
authors.lastname: Cardinal
authors.forename: Y
authors.initials: Y
authors.lastname: Labelle
authors.forename: N
authors.initials: N
authors.lastname: Laflamme
authors.forename: Y
authors.initials: Y
authors.lastname: Giguère
authors.forename: F
authors.initials: F
authors.lastname: Rousseau
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000483:Alleles; D004252:DNA Mutational Analysis; D005602:France / Q000208:ethnology; D005787:Gene Frequency; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D011792:Quebec / Q000453:epidemiology; D015203:Reproducibility of Results
chemical_list: D042964:Acyl-CoA Dehydrogenase