While diagnostic testing often results in a definitive answer for our patients, this testing can sometimes uncover genetic variation whose clinical significance is not clear. Most of the time, this is because this genetic variation has never been seen or investigated before. These variants (termed variants of uncertain significance or VUS) require further experimentation to functionally resolve their clinical importance.
One of the major roles of the GGC’s Research Division is to perform cell- and zebrafish-based functional studies, aimed at determining whether this genetic variation is in fact the cause of the patient’s symptoms. The value of these types of studies is manifold. First, we can confirm a genetic diagnosis, providing more concrete answers for our patients and their families, and for anyone who encounters the same variant after testing. Second, as more is understood about the genes being studied, the researchers can look for ways to harness this information towards the development of therapies. Once these studies are complete, the Research team works with the GGC clinicians and genetic counselors to share the information gained. They also communicate with the GGC Diagnostic directors to see if the variants can be formally reclassified as benign or disease-causing based on current American College of Medical Genetics guidelines.
Since 2018, GGC researchers (in collaboration with others around the world) have studied over 124 variants of uncertain significance in 40 different genes. These genes express proteins that can be found in all the different parts of the cell (see graphic below). Functional studies done at GGC have resulted in 10 publications.
Play peek-a-boo with 9 month-old Jeremiah Licorish of Florence, and you'll be rewarded with a huge grin that lights up both his and his mother's faces.
But this family has been through the unthinkable over the past few months, with very few reasons to smile.
At first things were going well. Jeremiah was a happy, healthy newborn, doted on by his mother, Aneesa, and his three big brothers. But when Jeremiah was around 5 months old, Aneesa noticed ...