Scientists at Columbia University recently published a study that helps better understand genetic changes linked to a rare immune condition called Activated PI3Kδ Syndrome (APDS). The study looked at over 2,000 different gene changes in two genes (PIK3CD and PIK3R1) to figure out which cause disease and which do not.
Many people who get genetic testing receive results called “variants of uncertain significance” (VUS), meaning doctors aren’t sure if those changes affect health. This new study helps clarify uncertain results by showing whether a gene change causes a pathway in the immune system to be overactive (working too much) or underactive (working too little).
This breakthrough has already helped a patient who had a VUS get a clear diagnosis of APDS. With this diagnosis, the patient was able to start treatment with leniolisib, a medicine approved by the FDA that targets the specific problem in APDS. Additional patients are expected to benefit from this study, as a significant number of individuals still carry VUSs that currently prevent a definitive diagnosis and access to treatment.
The study also suggests that APDS might be much more common than previously thought. By looking at large groups of people, researchers found that gene changes causing APDS could happen in about 1 in 5,000 people. Some of these people had immune or inflammation symptoms but were never diagnosed.
This new testing approach helps doctors move from uncertain genetic results to clear answers, which can lead to faster diagnoses and access to effective treatments like leniolisib. The researchers plan to use this method to study other rare immune diseases, hoping to bring better diagnosis and care to more patients.
Read the full press release here: https://www.cuimc.columbia.edu/news/new-method-speeds-diagnosis-rare-genetic-disease.