title: Regional differences in the frequency of the c.985A>G ACADM mutation: findings from a meta-regression of genotyping and screening studies.
abstract: Several countries include medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, a rare autosomal recessive disease, in their newborn screening programmes despite prevalence uncertainty. We estimated the frequency of its most common mutation, c.985A>G, tested for regional differences and compared screening and genotype frequencies. We identified 43 studies reporting the frequency of c.985A>G over 10 million individuals, and pooled frequency data using a novel Bayesian approach. We found significant variation in the frequency of the mutation across regions supporting a reported founder effect. The proportion of c.985A>G homozygotes was highest in Western Europe with 4.1 (95%CI: 2.8-5.6) per 100,000 individuals, then the New World (3.2, 95%CI: 2.0-4.7), Southern (1.2, 95%CI: 0.6-2.0) and Eastern European regions (0.9, 95%CI: 0.5-1.7). No cases with the mutation were identified in Asian and Middle Eastern regions. Significant differences were found in some countries between the genotype and screening allele frequency of c.985A>G. Our predictions could inform the frequency of the mutation by region and our approach could apply to other genetic conditions.
authors.affiliation: Health Economics Research Centre, University of Oxford, Oxford, UK.
authors.forename: J
authors.initials: J
authors.lastname: Leal
authors.forename: A E
authors.initials: AE
authors.lastname: Ades
authors.forename: S
authors.initials: S
authors.lastname: Wordsworth
authors.forename: C
authors.initials: C
authors.lastname: Dezateux
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D000483:Alleles; D005060:Europe; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D005838:Genotype; D060005:Genotyping Techniques; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D015997:Neonatal Screening; D016017:Odds Ratio
chemical_list: D042964:Acyl-CoA Dehydrogenase
keywords: MCAD deficiency; c.985A>G; inborn errors of metabolism; medium-chain acyl-CoA dehydrogenase deficiency