The limb-girdle muscular dystrophies (LGMD) are a group of genetically inherited, progressive, muscle-wasting diseases. Limb-girdle muscular dystrophies types 2A/R1 (LGMD2A/R1) and D4 (LGMDD4) are subtypes specifically caused by defects in the calpain 3 gene (CAPN3).
LGMD2A/R1
LGMD2A is the way the disease has been classified since its discovery, but LGMDR1 is an updated way to describe the same disease, with the R referring to the recessive mode of inheritance.
LGMDD4
More recently, researchers have observed that some families pass on the condition in a dominant mode of inheritance. This is called LGMDD4, with the D referring to dominant.
Collectively, these are called calpainopathy.
Calpainopathy is the most common form of limb-girdle muscular dystrophy, representing an estimated 20% of all LGMD cases. However, LGMD2A/R1 and LGMDD4 are still categorized as rare diseases. Scientists estimate that they affect about 1-5 in every 100,000 people.
Calpain 3 Gene
The CAPN3 gene provides instructions for making the calpain 3 enzyme in our bodies. The calpain 3 enzyme is a protein involved in the maintenance of muscle integrity and function.
When there is a mutation, or change, in the CAPN3 gene, it causes the enzyme to not work as it should, leading to the symptoms related to calpainopathy.
There are several theories about the function of calpain 3 and why mutations in CAPN3 cause muscular dystrophy, including its involvement in the process of muscle rebuilding. However, the exact role of calpain 3 in proper muscle functioning is not fully understood.