Author(s) :

Oliver Goulden.

Volume/Issue :

Abstract :

Population-specific variant data can improve genetic screening and interpretation, but reported frequencies are often drawn from evidence types that are not directly comparable. This narrative review examines the cystic fibrosis transmembrane conductance regulator (CFTR) gene in cystic fibrosis (CF), the MEFV innate immunity regulator (MEFV) gene in familial Mediterranean fever (FMF), and the beta-globin (HBB) gene in beta thalassemia across Irish, Mediterranean-associated, and Iranian populations. All numerical values discussed were extracted from published affected-patient cohorts, screening studies, systematic reviews, or public reference databases; they are not newly generated population estimates. Published Northern Irish CF cohorts show a concentrated CFTR mutation spectrum dominated by c.1521_1523delCTT (p.Phe508del), whereas the Iranian literature reports a broader range of CFTR variants. MEFV studies repeatedly identify c.2080A>G (p.Met694Val) across regional cohorts, but frequencies vary with referral patterns, testing panels, and population definition. Interpretation is also complicated by the debated penetrance of c.442G>C (p.Glu148Gln). For HBB, malaria-related selection provides a broad evolutionary explanation for the persistence of beta thalassemia, while local demographic processes may account for the regional predominance of particular pathogenic variants. The main limitations are non-equivalent denominators, referral and testing-panel bias, uneven geographic coverage, and the inability of frequency patterns alone to prove founder effects or selection. Overall, local mutation data are more clinically useful than broad ancestry labels and should be validated within the populations in which screening is performed.