Cystic fibrosis screening doesn’t catch all cases

3 minute read

About 10% of CF-causing genetic variants are missed, and East Asian parents are more likely to be affected.

Australian parents may fall through a gap in carrier screening that misses cystic fibrosis-causing variants in certain demographics.

The study, published in Prenatal Diagnosis, found that Australian reproductive carrier screening tests missed up to 10% of cystic fibrosis (CF) causing variants, disproportionately affecting people of East Asian descent. According to the 1000 Genomes Project, genetic classification for East Asian populations include China, Japan and Vietnam.

Researchers used longitudinal data from the Australian Cystic Fibrosis Data Registry from 1970 to 2020 to assess the effectiveness of current guidelines for CF carrier testing. Two commercially available Australian reproductive carrier screening tests were applied to the data of around 2500 individuals to identify if they carried pathogenic, or likely pathogenic classical CF-causing variants.

Results of the commercial screening tests were compared to comprehensive sequencing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is responsible for CF.

Study results showed that between 10% and 14% of CF variants would not be detected in people of European ethnicities, and that 100% of East Asian variants were not detected by the two commercial screening tests.

Dr Letitia Sng, CSIRO research scientist and co-lead author of the study, said Australian carrier screening guidelines recommend screening only the common variants that cause cystic fibrosis.

The current carrier screening methods appeared to be declining in sensitivity, she said.

“That might be due to the gap that missed 10% of CF-causing genetic variants. This is understandable considering the sort of immigration and demographic change Australia has been seeing,” Dr Sng said.

Study limitations included the inability to screen for novel intergenic pathogenic variants, and the inability to screen for rare CF variants from some structurally complex DNA rearrangements.

Dr Debra Kennedy is the director of MotherSafe at the Royal Hospital for Women. In 2016, she wrote in TMR that a brief discussion about family history – both maternal and paternal – was a vital part of a pre-pregnancy consultation.

“Information about ethnic background is relevant in terms of screening for certain conditions because of the higher carrier frequency in certain population groups,” she said.

Dr Kennedy also said that while pre-conception counselling allows potential parents to understand the possible risks, around 50% of pregnancies in Australia are unplanned.

Dr Sng said that although family history should be discussed in family planning consultations, many carriers might be unaware of their hereditary risk because CF can skip generations. She recommends a comprehensive CFTR carrier screening for people of East Asian ethnicities where possible.

Medicare does not rebate CF carrier screening fees for the general population. However, there are Medicare rebates for CFTR screening if referred by a specialist or consultant physician, and if the patient, or their relative, has a high probability of CF or CF-related disorder.

The study noted that in 2023 the Australian government intends to introduce a subsidy for carrier screening for CF, spinal muscular atrophy, and Fragile X syndrome.

However, under current guidelines, this subsidy will potentially perpetuate screening inequity for people of East Asian ethnicities.

Dr Sng said as the cost of CFTR analysis techniques has lowered, reproductive carrier screening guidelines in Australia could benefit from review.

“Current carrier screenings do very well. It’s just unfortunate that the gap disproportionately affects those of East Asian descent. This is an opportunity for medical guidelines to incorporate the changing demographics of Australia,” she said.

Prenatal Diagnosis 2022, online 15 December

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