Rare BMPR2 genetic variant linked to novel neurodevelopmental disorder and potential therapeutic targets

Researchers in Texas have identified a unique gain-of-function mutation in the BMPR2 gene that may explain previously undiagnosed developmental and behavioural issues, opening new avenues for targeted treatments.

Researchers in Texas have identified a rare genetic change in BMPR2 that appears to cause a newly recognised neurodevelopmental disorder, offering families a possible explanation for developmental difficulties that had previously gone unsolved. The study, published in The American Journal of Human Genetics and led by Texas Children’s Duncan Neurological Research Institute and Baylor College of Medicine, examined six unrelated children who shared the same variant.

Five of the children had global developmental delay affecting movement and speech or language, and four were diagnosed with autism spectrum disorder. Some also had seizures, anxiety or hyperactivity. According to the research team, the finding matters not only because it links the same variant to similar symptoms in different children, but because it points to a specific biological pathway that may be relevant to future therapies.

BMPR2 encodes a receptor on the cell surface that helps transmit signals involved in growth and development. The gene is already known for a different kind of disorder: loss-of-function changes can cause pulmonary arterial hypertension, a serious condition affecting blood vessels in the lungs, according to the National Centre for Biotechnology Information. In this case, however, the variant acted in the opposite way, leaving the receptor overly active even when no signal was present. That makes it a gain-of-function change, a term used when a gene becomes too active rather than too weak.

To understand the effect, the researchers recreated the human variant in fruit flies, a common model for studying disease genes. The flies showed excessive BMP signalling and abnormal nervous system development. In neurons, the variant increased the number of synaptic connections; in glial cells, which support and protect nerve cells, the effect was stronger and more disruptive. The team also reported that two experimental compounds reduced the abnormal signalling in fly tissue, an early result that could help guide further work, though the researchers stressed that these are research tools, not treatments.