Researchers link a rare BMPR2 change to childhood developmental disorders.
Researchers have identified a rare genetic change that may explain a newly recognized developmental disorder in children. The discovery, led by scientists at Texas Children’s Duncan Neurological Research Institute and Baylor College of Medicine, offers new information about how certain genetic changes can affect brain development. It could also help families whose children have experienced developmental challenges without receiving a clear diagnosis. The study, published in The American Journal of Human Genetics, examined six unrelated children who shared the same rare change in a gene called BMPR2. This gene plays a role in sending signals that help cells grow and develop. Researchers found that the children experienced several overlapping conditions, including developmental delays, autism and, in some cases, seizures, anxiety or hyperactivity.
Five of the six children had global developmental delays that affected areas such as movement and speech or language. Four had received an autism spectrum disorder diagnosis. The shared genetic finding gave researchers a reason to investigate whether the change could be responsible for the children’s difficulties. The BMPR2 gene normally helps control a signaling system known as the bone morphogenetic protein (BMP) pathway. This pathway supports several biological processes, including the development of the brain and nervous system. Under normal conditions, BMPR2 receives signals from outside a cell and helps pass instructions inside it.
However, the genetic change identified in the children appears to make the BMPR2 receptor too active. Rather than reducing its activity, as some other genetic changes can do, this variant causes it to send excessive signals, even when the usual activating signal is absent. Scientists describe this type of change as a gain-of-function variant. The finding is notable because other changes involving BMPR2 are already linked to pulmonary arterial hypertension, a serious condition affecting blood vessels in the lungs. Those changes can reduce the gene’s activity. The newly identified variant appears to have the opposite effect, showing how changes within the same gene can produce different health conditions.
To better understand how the variant affects the nervous system, the research team recreated the human genetic change in fruit flies. These insects are commonly used in genetic research because many biological processes can be studied through their genes and development. The experiments showed that flies carrying the variant had excessive BMP signaling and abnormal nervous system development. When the altered gene was active in neurons, the flies developed too many synapses, which are connections that allow nerve cells to communicate.
Researchers also examined the effects of the variant in glial cells. These cells support and protect neurons and help maintain a healthy environment within the brain. When the genetic change was active in glial cells, the flies experienced a much stronger increase in BMP signaling and severe developmental effects. The results suggest that the disorder may involve more than one type of brain cell. Understanding which cells are affected could help researchers learn more about how the condition develops and why children may experience different symptoms.
The team also tested two experimental compounds developed at Baylor College of Medicine’s Center for Drug Discovery. In isolated fly tissues, both compounds reduced the excessive BMP signaling caused by the genetic variant. Researchers stressed that the compounds are experimental research tools and are not ready for use as treatments in patients. Further testing will be needed to determine whether the pathway can be safely targeted and whether similar results can be achieved in more advanced research models.
Future work may also help determine which brain cells are most affected and whether treatments could eventually be developed to control the excessive signaling. For families affected by unexplained developmental conditions, the discovery provides a possible genetic explanation and a starting point for further research.
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Researchers identify a rare genetic change linked to neurodevelopmental disorder
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