The inequity of targeted cystic fibrosis reproductive carrier screening tests in Australia.

Objective: European and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia. Methods: Next‐generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis. Results: Variant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test. Conclusions: Reproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation. Key points: What's already known about this topic? Reproductive carrier screening for cystic fibrosis (CF) is becoming increasingly common in Europe and Australia. European and Australian guidelines recommend testing for a targeted set of the most common CF causing variants. What does this study add? Reproductive carrier screening tests for a targeted set of CF causing variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population and individuals of East Asian ethnicity are disproportionally affected by this limitation of the test. [ABSTRACT FROM AUTHOR]