Exploring the diversity of CFTR gene mutations in cystic fibrosis individuals of South Asia

Abstract

Objective: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. This study aimed to identify the spectrum of CFTR variants reported in individuals with CF from South Asia (ISA).

Data sources and study selection: We conducted a PubMed search for CFTR variants reported in ISA. Full text of original articles and case reports was read to compile data on reported variants. To gather additional data, we independently cross-referenced each variant with the CFTR Mutation Database and ClinVar.

Results: Our investigation identified a total of 92 CFTR variants reported across 30 articles. The most frequently tested, and reported variant was ΔF508 with a global frequency of 69.74%. Notably, we found 14 pathogenic CFTR mutations shared among ISA, originating from more than one South Asian country: ΔF508, 1525-1 G > A, G542X, S549N, R117H, S549R, R709X, V456A, Y569D, L1077P, 1161delC, 1898 + 1 G > T, G551D, and 2184insA.

Conclusion: In summary, the higher prevalence of consanguinity and the limited availability of CF diagnostic resources in South Asia considerably contribute to the prevalence of genetic disorders like CF. The spectrum of CFTR mutations exhibits noticeable variations within South Asian and other populations. The inclusion of current study-enlisted CFTR gene variants is highly recommended for CF disease genetic testing in South Asia which may aid in achieving a precise diagnosis, enhancing disease management, and discovering drugs for currently untreatable genetic variants. It is also imperative to conduct a comprehensive study in this region, especially in previously unexplored countries such as Nepal, Bhutan, Maldives, and Bangladesh.

Keywords: Afghanistan; CFTR variants; India; Iran; Pakistan; South Asia; Sri Lanka; cystic fibrosis.