Cystic fibrosis carrier screening in Australia: comparing sequencing and targeted panels across diverse ancestries

Background: Targeted cystic fibrosis (CF) carrier screening panels may lack sensitivity in non-European ancestry groups. This study aims to evaluate the sensitivity of various panels in Australian CF carriers identified through sequencing.

Methods: The following panels were evaluated in 869 CF carriers: Asuragen, Elucigene, Devyser, American College of Medical Genetics and Genomics and Victorian Clinical Genetics Services. Ancestry-specific CF carrier frequencies from population databases and Bayesian analysis were used to estimate post-test residual carrier risks.

Results: When variants with varying clinical consequences (VCC) were not considered, mean test sensitivity was highest in the Northern Europe group (95.6%) and lowest in the Southern Asia group (64.0%). The post-test residual carrier risk in the Northern Europe group was approximately 1 in 546, with only the Southern Asia group having a higher residual carrier risk of 1 in 179.

Conclusion: The Southern Asia group exhibited the lowest test sensitivity and the highest post-test residual carrier risk, surpassing that of the Northern Europe group. The inclusion or exclusion of VCC significantly impacted the calculated test sensitivities. Further research is suggested to better characterise CFTR variants in non-European ancestry groups and to determine which VCC, if any, should be included in carrier screening reports.