School of Pathology (ETDs)

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    Cystic fibrosis: An update on the variant profile and carrier frequency in the Black South African population
    (University of the Witwatersrand, Johannesburg, 2024) Smit, Ingrid; Essop, Ms F.
    Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the CFTR gene. Limited genetic research has been conducted on the Black South African population, and molecular testing is frequently the only way a diagnosis can be made. At the NHLS, testing is performed for the common 3120+1G>A (c.2988+1G>A) variant in the Black population, and other common European CF variants. Recent studies in the Division of Human Genetics show evidence of other recurrent CFTR variants. The aim of this study was to screen for these and other variants to update the CFTR variant profile and carrier frequency in the Black population. NGS data on 395 unaffected individuals was used for CFTR variant identification, annotation, prioritisation, and classification using the ACMG-AMP guidelines. The c.2988+1G>A variant accounted for 36.4% of CF alleles, which is less than previously reported (46%), suggesting that there are other common CF-causing variants in this population. The recurrent variants previously identified were not detected in this cohort, possibly due to limitations in NGS, the bioinformatic pipeline, or small sample size. Three novel likely pathogenic variants (c.3392T>C, c.3038C>G, and c.2594G>C) were identified, with carrier frequencies of 1 in 395 each, which could potentially be African-specific variants. Identifying these variants, not currently included in commercial panels, allows for targeted molecular testing in this population group. Additionally, a revised CF carrier rate of 1 in 36 was estimated which is consistent with literature, highlighting the accuracy of NGS data for carrier screening, leading to accurate risk counselling