Brody myopathy (Brody myopathy) - Gen ATP2A1.
Brody myopathy is a disorder that affects the skeletal muscles. Affected individuals have muscle cramps and stiffness after exercise or other strenuous activity, especially in cold temperatures. Usually, these symptoms begin in childhood and are painless, but in some cases may cause mild discomfort. Muscles usually relax after a few minutes of rest. The muscles most often affected are the muscles of the arms, legs and face, especially the eyelids. In some people with Brody myopathy, exercise leads to rhabdomyolysis. The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidney and released into the urine (myoglobinuria). Myoglobin makes the urine red or brown.
This process is due to mutations in the gene ATP2A1, located on the short arm of chromosome 16 (16p12.1). This gene encodes the enzyme SERCA1, belonging to a family of enzymes that help control ATPase level of calcium ions inside cells. The SERCA1 enzyme found in skeletal muscle cells. Within muscle cells, the enzyme SERCA1 is in the sarcoplasmic reticulum, which plays an important role in muscle contraction and relaxation by the storage and release of calcium ions. When calcium ions are transported out of the sarcoplasmic reticulum, the muscles contract, while when calcium ions are transported into the sarcoplasmic reticulum, the muscles relax. The enzyme SERCA1 transports calcium ions from the sarcoplasmic reticulum cell in causing muscle relaxation.
They have identified at least 10 ATP2A1 gene mutations that result Brody myopathy. Most mutations result in premature stop signal encoding the enzyme SERCA1, resulting in a nonfunctional enzyme. Other mutations lead to SERCA1 encoding an enzyme with decreased function. As a result, calcium ions are slow to enter the sarcoplasmic reticulum and muscle relaxation is delayed. After exercise or other strenuous activity, during which the muscles contract and relax rapidly, affected people develop muscle cramps because your muscles can not relax. It is likely that other proteins or other means to act in the absence of an enzyme SERCA1 fully functional for the transport of calcium ions in the sarcoplasmic and help with muscle relaxation reticulum.
Brody myopathy generally inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. Some people with Brody myopathy autosomal recessive mutation are not identified in the ATP2A1 gene. In these cases, the cause of the disease is unknown.
Tests in IVAMI: in IVAMI perform detection of mutations associated with myopathy Brody, by complete PCR amplification of exons ATP2A1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).