Overview
- The finding was published Monday in the American Journal of Human Genetics after researchers combined AI prioritization, international matching and lab studies to study 10 affected people from seven unrelated families.
- AI-MARRVEL flagged a rare BRSK1 change in a child tested through the Texome Project when standard trio analysis found no diagnosis, and GeneMatcher helped assemble the wider cohort.
- All individuals had developmental delay and a mix of features that varied widely, including delayed speech, intellectual disability, autism traits, ADHD, low muscle tone, microcephaly and seizures in two people.
- Fruit fly experiments showed the fly BRSK1 equivalent (sff) is neuronally expressed and essential for normal movement and seizure resistance, that normal human BRSK1 largely rescues fly defects, and that three patient-derived variants give only partial rescue while raising levels of the microtubule-associated protein Futsch.
- The work offers a diagnostic answer for affected families and shows how AI plus model-organism validation can find rare-disease genes, although authors say larger cohorts and deeper studies are needed to define penetrance, explain variable symptoms and clarify therapeutic implications.