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Resources for Medical Professionals

We serve two communities: parents whose children have been diagnosed with the mutation and the medical community caring for our children and researching the mutation. Together, we are working towards a treatment and a cure.

Overview

PPP3CA Developmental Epileptic Encephalopathy (DEE91) is an ultra-rare genetic disorder caused by variants in the PPP3CA (protein phosphatase 3 catalytic subunit alpha) gene. The PPP3CA protein is a subunit for calcineurin which typically works to regulate synaptic vesicle recycling at nerve terminals and is especially abundant in the brain regulating development, synaptic plasticity, learning and memory formation. This protein is involved in the synapse regions between nerve cells. It plays a role in "recycling" the vesicles which carry the neurotransmitters. It is also important in brain development, connectivity and regulating electrical activity.

 

Three distinct phenotypes have emerged depending on where the variant is located within the gene: catalytic, regulatory, or autoinhibitory domain. Symptoms may overlap between phenotypes and include refractory epilepsy, autism spectrum disorder, low muscle tone, challenging behaviors, brain abnormalities, dysmorphic features and skeletal dysplasia. All individuals have developmental delays / intellectual disabilities; many are severely impacted.

The genetic mutations lead to either a Loss of Function (LoF) or a Gain of Function (GoF) in the protein. A LoF is a genetic change that reduces of eliminates the activity or function of the gene or its protein product. This can occur in various ways, such as by reducing the amount of protein produced, altering its stability or changing its activity. A GoF is a genetic change that leads to an increase in the activity or function of the gene or its protein product. This can occur in various ways, such as by increasing the amount of protein produced, altering its stability or changing its activity. Mutations in the PPP3CA gene have shown to result in LoF or GoF depending on where the mutation occurs.

To learn more about the most up-to-date medical information see links below:

Medical Professionals Kit

Clinical Fact Sheet

Research Papers

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