Q: What is PPP3CA?
A: PPP3CA (protein phosphatase 3 catalytic subunit alpha) is a protein-coding gene that provides instructions for making part of calcineurin, a calcium-dependent enzyme highly active in the brain.
In 2017, research first established that variants in this gene are associated with a neurodevelopmental disorder known as PPP3CA-related developmental and epileptic encephalopathy (DEE91). These variants can disrupt normal brain signaling and development, leading to epilepsy and developmental challenges.
Research in this area is rapidly evolving, and the PPP3CA community is working to accelerate progress toward targeted treatments.
Q: What is whole exome sequencing?
A: Whole exome sequencing (WES) is a genetic test that analyzes the protein-coding regions of approximately 20,000 genes in the human genome. It looks for changes in DNA, including: single letter (spelling) changes, small insertions or deletions, and in some cases, large deletion or duplications of genetic material. WES is one of the most common tools used to diagnose rare genetic disorders like PPP3CA.
Q: How are children with a PPP3CA genetic mutation generally diagnosed?
A: PPP3CA is diagnosed through genetic testing, most often through whole exome sequencing, whole genome sequencing, or epilepsy gene panels.
Children are typically evaluated due to symptoms such as early-onset epilepsy, global developmental delays, hypotonia, and autism spectrum features or behavioral differences.
As awareness and access to testing increase, more individuals are being identified worldwide. The condition remains underdiagnosed.
Q: What does de novo mutation mean?
A: A de novo mutation means that the genetic change is new in the child and is not found in either parent’s DNA. These variants occur spontaneously and are a common cause of many rare neurodevelopmental disorders.
Q: Is this community researching any other disorders or genetic mutations?
A: No. The PPP3CA Hope Foundation™ is exclusively dedicated to PPP3CA-related disorders, with a focus on advancing research, supporting families, and accelerating the development of targeted treatments.
Q: How is the PPP3CA Hope Foundation™ helping?
A: Founded in 2022, The PPP3CA Hope Foundation™ is a non-profit charity dedicated to funding scientific research, supporting families and building community, raising awareness of PPP3CA, and accelerating a path toward targeted treatments.
Q: How does it affect children?
A: PPP3CA disorders affect the brain and nervous system. While each child is unique, commonly reported features include: developmental delays and intellectual disability, epilepsy, hypotonia (low muscle tone), autism spectrum features and behavioral challenges, feeding difficulties and growth concerns. There is a wide spectrum of severity, even among individuals with similar variants.
Q: Who is conducting the research?
A: The foundation supports and collaborates with leading researchers studying calcineurin biology, neurodevelopment, and epilepsy. Please refer to our Research and Partnerships pages to learn more.
Q: How will funds raised by the PPP3CA Hope Foundation™ be used?
A: Donations directly support research efforts, including understanding how PPP3CA variants affect brain function, developing disease models, and identifying and testing potential targeted therapies. Every contribution helps move research forward.
Q: What is the timeline for treatments?
A: Developing treatments for rare diseases is a multi-step process and can take 10+ years. While timelines vary, research generally progresses through early discovery and disease modeling, identification of therapeutic targets, preclinical testing, and clinical trials. Each phase can take three to five years to complete. The foundation’s goal is to accelerate this timeline through focused funding and collaboration.
Q: What are iPSCs (induced pluripotent stem cells) and why are they important?
A: Induced pluripotent stem cells (iPSCs) are created from a patient’s skin or blood cells and can be turned into different cell types, including neurons. They allow researchers to study how PPP3CA variants affect human brain cells and test potential treatments directly on patient-derived cells. This is a powerful tool for developing precision therapies.
Q: How can I help?
A: Families: Contact us to join our community, participate in the PPP3CA registry, and enroll in research platforms like Simons Searchlight. Supporters: Donate, fundraise, and help raise awareness. Your support helps advance research and bring us closer to effective treatments for children living with PPP3CA. Our children are waiting.