ORLANDO, Florida (GenomeWeb) – Carrier results for newborns enrolled in the BabySeq project have led some parents to seek their own genetic testing in order to inform their reproductive plans, according to a presentation at the American Society of Human Genetics annual meeting here today. In addition, the BabySeq study picked up many carrier variants in genes not covered by a commercial carrier screening test, suggesting that current screening panels might need to be expanded.
The BabySeq project, led by researchers at Brigham and Women's Hospital and Boston Children's Hospital, was launched in 2013 to study how genomic sequencing could be applied in the newborn setting and how it would impact families and healthcare providers.
The project is run as a randomized clinical trial with two cohorts: healthy infants and sick newborns in the intensive care unit. All of them receive the standard of care, including state-mandated newborn screening, and half the infants additionally receive exome sequencing.
Three types of results are returned to families: pathogenic or likely pathogenic variants in monogenic disease genes, carrier status information for recessive conditions, and pharmacogenomics results.
According to Casie Genetti, a researcher at Boston Children’s Hospital, exome sequencing for 125 babies has been completed to date. Of these, 109 (87 percent) had at least one, and up to six, carrier results for an autosomal recessive disorder. In total, the researchers found 232 such variants in 166 genes and several genes came up more than once in their cohort, she added.
Variants in the gene BTD, which is associated with biotinidase deficiency, were revealed in 12 cases, which Genetti said was a somewhat unexpectedly high rate. Other genes for which they found variants in more than one newborn included GJB2, which is linked to non-syndromic hearing loss; RBM8A, which is connected to thrombocytopenia absent radius syndrome; the cystic fibrosis gene CFTR; ABCA4, which is associated with Stargardt macular degeneration; and MUTYH, which is linked to attenuated familial adenomatous polyposis.
The researchers then looked how many of the 166 genes for which they found carrier results would have been picked up by the Counsyl Family Prep Screen (recently renamed the Foresight Carrier Screen), a commercial sequencing panel test that screens for carriers of more than 175 actionable diseases.
They found that only 38 of the 166 genes were included in the commercial test, meaning that 77 percent of the genes they reported would have been missed. This included three of the genes for which they found variants in multiple individuals, she noted, suggesting that such genes should possibly be included in commercial offerings.
The researchers followed up with a survey 10 months after parents received the carrier status information for their infants. According to the survey, 11 percent of parents had decided that, based on the test results, they would pursue genetic testing for themselves in order to be able to better plan future pregnancies.
Genetti pointed out one case in particular where the newborn was found to be a carrier of four disease-associated variants, including one in the CTNS gene, which is linked with nephropathic cystinosis. The parents decided to pursue their own carrier testing and found that they were both carriers of a CTNS mutation. As a result, they considered preimplantation genetic diagnosis for a subsequent pregnancy, which would enable them to rule out that their child would be affected by the disease.
Overall, Genetti said, returning carrier information as part of the BabySeq project appears to not only benefit the child in the future, but also, more immediately, his or her parents.