番茄社区

Couples who were found to be genetic carriers for autosomal recessive or X-linked genetic conditions often opted to change their reproductive strategy, a large Australian population-based study found.

Overall, 1.9% of the 9,107 couples tested had an increased chance of having a child with certain genetic conditions, and 76.6% of these couples subsequently said they used or planned to use reproductive interventions, according to Martin Delatycki, MBBS, PhD, of Victorian Clinical Genetics Services in Australia, and colleagues.

Those with an increased risk of having a child with certain genetic conditions also reported greater anxiety than those who had a low chance, they .

"Our guiding principle was that we wished to identify reproductive couples at risk of having children with serious childhood onset conditions or where early intervention can improve outcomes," Delatycki told 番茄社区, noting that technological advances in the past few decades have made it possible to test for thousands of genes at once. The team decided on about 1,300 autosomal and X-linked recessive genes that underlie about 750 conditions.

For 45 couples who found out their increased risk, the woman was pregnant, and 29 opted to have the fetus genetically tested; five found abnormal results and four opted to end the pregnancy. Meanwhile, among the 130 couples with increased risk where the female was not pregnant at time of testing, 95 (73.1%) said they planned to use in vitro fertilization with preimplantation genetic testing for monogenic conditions.

Still, decisional regret was low across all groups; 98.9% said the screening was acceptable.

In 2017, an Australian couple lost their baby daughter Mackenzie to spinal muscular atrophy. After that tragedy, they advocated for access to reproductive carrier screening, forming a nationwide genetic carrier screening project called Mackenzie's Mission, which the Australian government funded to the tune of $20 million. Genetic carrier screening has been available in Australia for a while, but individuals had to pay for the service and the majority of people were not offered it. Delatycki also noted that free carrier screening for cystic fibrosis, spinal muscular atrophy, and fragile X syndrome is now available for Australians planning pregnancy.

"In our study, 80% of the newly identified increased chance couples were for conditions other than these three, emphasizing how important it is to screen for a greater number of conditions," he said.

In an , Lidewij Henneman, PhD, of the department of human genetics at Amsterdam University Medical Center in the Netherlands, wrote that this study "provides lessons on how to implement carrier screening in practice" and can "inform a global research agenda" despite not being directly translatable to other countries and contexts.

Henneman also encouraged monitoring "long-term psychological and reproductive outcomes of those who have undergone screening."

The study investigated the feasibility and outcomes of a nationwide, couple-based genetic carrier screening program. In total, 10,038 reproductive couples enrolled and were offered genetic carrier screening testing for at least 1,281 genes before pregnancy or early in pregnancy, of which 9,107 (90.7%) completed screening.

Couples self-administered saliva swabs and sent the samples to a lab. Genetic counseling was provided if either person was found to be a carrier of an autosomal or X-linked condition. Three quarters (74.3%) of the conditions were autosomal recessive and stemmed from pathogenic variants in 90 different genes.

Looking forward, the team is working with the Australian government to figure out what it would take to make genetic carrier screening free for any Australian wanting to utilize that service.

The authors noted a few limitations, including that in standard approaches to screening for fragile X syndrome, "most identified premutations are small expansions of triplet repeats, with a low, perhaps zero, likelihood of expansion to a full mutation in a transmission," which can lead to unnecessary reproductive interventions. The study also limited reporting to variant combinations tied to serious childhood-onset conditions in which an early intervention could improve prognosis and thus didn't focus on variants known to result in mild conditions or adult-onset conditions.

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