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Australian Study Highlights Carrier Screening Impacts in Reproductive Context

NEW YORK (GenomeWeb) – A large screening study performed in Australia has provided a look at the frequency of carrier status for three conditions in that population, while demonstrating ties between reproductive screens and diagnoses in pregnancy.

For a paper appearing in in Genetics in Medicine yesterday, researchers at Victorian Clinical Genetics Services (VCGS), a non-profit subsidiary of Murdoch Children's Research Institute, and other centers in Australia shared findings from a carrier screening study of 12,000 individuals in Melbourne and other parts of Victoria state. In that population, they identified 610 carriers for the autosomal recessive or X-linked conditions considered: cystic fibrosis, fragile X syndrome, and spinal muscular atrophy.

The team's carrier screens — offered in general medicine, obstetrics, fertility, or genetics settings — identified 50 couples with elevated risk of having a child with one of the conditions, including 32 couples already expecting a child. More than two-dozen couples proceeded with prenatal diagnostic testing, which revealed four cases of cystic fibrosis, two fragile X syndrome fetuses, and one prenatal spinal muscular atrophy diagnosis.

"Our program revealed approximately one in 20 individuals to be a carrier of one or more of the conditions tested, and for the majority there was no known family history of the condition," VCGS researchers Alison Dalton Archibald and Melanie Jane Smith, the study's co-first authors, and their colleagues wrote.

They noted that the "high proportion of individuals identified as carriers emphasizes the benefits of implementing a population-based carrier screening approach rather than relying on family history to guide screening decisions."

For their carrier screen, the researchers relied on the VCGS "prepair" protocol, which uses approaches such as mass spectrometry, triplet repeat primed PCR, capillary electrophoresis, and/or quantitative real-time PCR to search for disease-associated variants in the CFTR, FMR1, and SMN1 genes (implicated in cystic fibrosis, fragile X syndrome, and spinal muscular atrophy, respectively). The test comes with a price tag of AUD$385 ($295) and aims to report results in 10 days.

Their screen identified 342 cystic fibrosis carriers, 35 individuals carrying FMR1 repeat expansions associated with fragile X syndrome, and 241 individuals deemed spinal muscular atrophy carriers. Eight individuals were carriers for two of the conditions.

The team initially focused on female participants, but expanded their search to affected partners when a carrier mutation was found. In the case of cystic fibrosis, the group screened 319 partners of known carriers to narrow in on 14 couples who were both carriers, including nine expectant couples. Follow-up diagnostic tests indicated that four pregnancies were affected by cystic fibrosis.

The researchers also did partner testing for 233 spinal muscular atrophy carriers, narrowing in on one pregnant carrier couple with a fetus diagnosed with the condition. Meanwhile, their fragile X syndrome-focused screen ultimately led to two affected pregnancies, while at least two fragile X carriers experienced miscarriages.

All of the fragile X carriers and carriers of spinal muscular atrophy or cystic fibrosis who had carrier partners were referred for genetic counseling to discuss the genetic, clinical, and potential reproductive consequences of carrier status.

"Offering screening through a coordinated clinical and laboratory service ensures patients are supported to make informed reproductive choices," the authors wrote. Based on their findings, they argued that "despite individual recessive conditions being relatively rare, when tested collectively, the combined chance of an affected child with one of the conditions is comparable to that of Down syndrome."