
Studies show for the first time how functional tests can clarify genetic false alarms and protect families from irreversible therapies and substantial costs
Photo Credit: Griffith University
Scientific Frontline: "At a Glance" Summary
- Main Discovery: Routine newborn screening for spinal muscular atrophy can produce false positive results due to undetected, functional variants of the SMN1 gene, which masquerade as an absent genetic trigger.
- Methodology: Researchers inserted patient-specific SMN1 gene variants from two human infants into a zebrafish embryo model lacking a functional homologous SMN1 gene to observe whether the animals developed associated motor deficits or remained healthy.
- Key Data: Withholding unnecessary spinal muscular atrophy therapies saved an estimated $2 million in medical costs per infant, with both subjects demonstrating normal motor skill development at two years of age.
- Significance: Rapid functional testing of genetic variants clarifies ambiguous screening results, effectively preventing the administration of premature, irreversible, and highly expensive therapeutic interventions on healthy children.
- Future Application: Zebrafish-based functional assays can be deployed to efficiently classify genetic variants of unclear significance during neonatal screening for various rare congenital diseases.
- Branch of Science: Medical Genetics, Molecular Medicine, and Pediatrics.
- Additional Detail: The functional analyses and epidemiological findings were validated by a collaborative international team and published in the American Journal of Human Genetics and EMBO Molecular Medicine.
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