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

Abstract

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.

Antenatal Screening for CFTR Variants—Reply

“…Carrier screening with CFTR genetic panels tests for a small number of high-frequency pathogenic cystic fibrosis variants. Antenatal genetic screening is not immune to inequities, as previously noted in observations of the selection of newborn screening genetic panels . Clinicians involved in prenatal screening and family planning should consider limitations of antenatal detection from a narrow subset of CFTR pathogenic variants and discuss a role for more comprehensive testing for pan-ethnic carrier screening to address potential inequities…”