SNP Shot: Genomic Insights

Tubular aggregate myopathy is a condition that mainly affects the skeletal muscles, which are responsible for body movement. This condition results in muscle pain, cramps, or weakness that starts in childhood and progressively worsens. The muscles of the legs are usually the most affected, but the arms can also be involved. People with this condition may find it difficult to run, climb stairs, or rise from a squat. The weakness can also cause an abnormal walking pattern (gait). Some individuals develop joint deformities (contractures) in their arms and legs.

Typically, skeletal muscles contain roughly equal amounts of two types of fibers: type I and type II. Type I fibers, also called slow-twitch fibers, are used for endurance activities like long walks. Type II fibers, or fast-twitch fibers, are used for short bursts of power, like running upstairs or sprinting. In tubular aggregate myopathy, the type II fibers deteriorate (atrophy), leaving affected individuals with predominantly type I fibers. Furthermore, abnormal protein accumulation occurs in both fiber types, forming clusters of tube-like structures called tubular aggregates. While tubular aggregates can be present in other muscle disorders, they are the main muscle cell abnormality in tubular aggregate myopathy.

Inheritance:

Most cases of tubular aggregate myopathy, including those caused by mutations in the STIM1 gene, are inherited in an autosomal dominant manner. This means that having only one copy of the mutated gene in each cell is enough to cause the condition. In some families, the mutation is passed down through generations. However, in other cases, the mutation arises spontaneously and occurs in individuals with no family history of the disorder. In rare instances, tubular aggregate myopathy follows an autosomal recessive inheritance pattern. This means that both copies of a gene in each cell must have mutations for the condition to develop. The parents of a person with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not exhibit any signs or symptoms of the condition. Researchers are still trying to identify the gene(s) responsible for autosomal recessive tubular aggregate myopathy.