Reproductive carrier testing is an important tool for well-informed family planning especially for inherited recessive disorders like cystic fibrosis. Our recent Prenatal Diagnosis publication in collaboration with Genepath showed that current screening recommendations are limited, disproportionately affecting Australian carriers of East Asian descent.

Cystic Fibrosis (CF) is an inherited disorder of the production of saliva, sweat, and mucus due to mutations in the CFTR gene. People with CF develop abnormal amounts of thick and sticky mucus particularly in the lungs that can cause recurrent bacterial infections, ultimately leading to lung damage and respiratory failure. There is currently no cure for CF and management and treatment of CF symptoms is lifelong, intensive, and constant.

As an autosomal recessive disorder, the mutations in the CFTR gene need to be inherited from both parents. Therefore, if both parents are carriers of a single mutation, their children have a 25% chance of being born with CF. In Australia, the carrier rate for CF is 1 in 34. Importantly, carriers are unaffected by CF and are usually unaware of their carrier status, highlighting the importance of carrier testing for well-informed family planning.

Current recommendations for Australian reproductive carrier screening tests by the Human Genetics Society of Australasia (HGSA) are for a panel targeting at least 17 of the most common high penetrance variants in the CFTR gene, and sequencing of the CFTR gene is not recommended. This means that recommended panel tests look for only 17 of the hundreds of  'spelling mistakes' in the DNA code of the CFTR gene that can cause CF.

We have recently published work on a targeted gene sequencing approach to reproductive carrier screening in cystic fibrosis in Australia in collaboration with Australian biotech start-up, GenePath. The study compared the use of a sequencing approach to cystic fibrosis screening over existing recommended panels tests. Using the Australian Cystic Fibrosis Data Registry, we found that current detection rates of panel screening tests are and have historically been high (up to 88.2%) but sensitivity has been significantly decreasing in the last 10 years. Crucially, the gap in detection rates of about 10% disproportionately affects carriers of East Asian descent in a multiethnic Australian population.

As Australia’s demographics continue to diversify due to increase immigration from non-European countries like India and China, our findings suggest that guidelines for reproductive carrier screening should be reviewed considering the cost effectiveness of sequencing approaches to benefit all Australians.

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