Coalition to Cure Calpain 3 (C3) is pleased to announce a research grant has been awarded to Dr. Svetlana Gorokhova, working together with Dr. Marc Bartoli in the Translational Neuromyology Team, Marseille Medical Genetics Institute at Aix Marseille University. The project,“A diagnostic functional test to rule out dominant forms of calpainopathy,” will develop a tool to help identify the inheritance patterns of CAPN3 variants.
Calpainopathy is a form of limb-girdle muscular dystrophy (LGMD) caused by variants in the CAPN3 gene that encodes the protein calpain 3. Most people with calpainopathy have LGMD2A/R1, which is inherited in a recessive pattern. This means that individuals must have two copies of the abnormal gene for LGMD2A/R1, one inherited from the mother and one from the father, to develop. Several recent reports show that less commonly, calpainopathy is inherited in a dominant manner. This is called LGMD1I/D4 and only needs a single copy of the abnormal gene for individuals to develop muscular dystrophy. You can read more about calpainopathy inheritance here.
Since calpainopathy can be inherited in both recessive and dominant ways, it can be challenging to diagnose an individual with limb-girdle weakness who has only one CAPN3 variant identified: should one continue searching for a second variant or conclude that this patient has the dominant form of the disease? Dr. Gorokhova and her colleagues aim to develop a diagnostic functional assay that could answer if a single variant can cause the dominant form of calpainopathy. This test could help individuals with only one CAPN3 variant get a genetic diagnosis much faster, allowing more efficient disease management and possibly facilitating inclusion in future clinical trials.
It is critical that individuals with LGMD get a genetic confirmation of their diagnosis.