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Regional differences in the frequency of the c. 985A >G ACADM mutation: findings from a meta‐regression of genotyping and screening studies
Author(s) -
Leal J.,
Ades A.E.,
Wordsworth S.,
Dezateux C.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12157
Subject(s) - allele frequency , genotype , genotyping , mutation , genetics , allele , biology , meta analysis , mutation frequency , medicine , demography , gene , sociology
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.