Miyoshi myopathy (Miyoshi myopathy) - Genes DYSF or Year5
Miyoshi myopathy, muscular dystrophy also called Miyoshi, a muscle disorder that primarily affects the distal muscles, as the leg muscles. In general, the early and mid-adulthood, those affected have weakness and atrophy in one or both calves, causing inability to stay on your toes, climbing stairs and running. As the disease progresses, muscle weakness and atrophy extend the leg muscles of the thigh and buttock. Finally, affected individuals may have difficulty climbing stairs or walking for a long time. Some of these individuals may eventually need a wheelchair. Rarely, malarial illness can affect the upper muscles of the arms or shoulders. In a few cases, individuals have arrhythmias. People with Miyoshi myopathy have very high concentrations in the blood of an enzyme called creatine kinase (CK), which often indicates a muscle disease.
Miyoshi myopathy is due to mutations in the DYSF (dysferlin) gene or gene Year5 (anoctamin 5). When Miyoshi myopathy is due to mutations in the gene DYSF known as disferlinopatía, it lies that when due to mutations in the gene is termed Year5 sometimes distal anoctaminopatía. These genes encode proteins which are located primarily in skeletal muscles.
The DYSF (dysferlin) gene, located on the short arm of chromosome 2 (2p13.2), encoding dysferlin protein, located at the sarcolemma surrounding muscle fibers. It is believed that this protein helps in repairing sarcolemmal when damaged, or torn, due to muscular tension. It is believed that dysferlin may also be involved in regeneration of the muscle fibers and inflammation, but little is known about these functions. They have identified more than 100 mutations in the gene that cause DYSF Miyoshi myopathy. Mutations in the gene DYSF identified in people with Miyoshi myopathy change amino acids in the protein dysferlin, disrupting the function of the protein or results in encoding a nonfunctional protein. A common mutation in people of Japanese descent replaces the amino acid tryptophan amino acid cysteine at position 999 Dysferlin (Trp999Cys or W999C). The lack of Dysferlin, results in a decreased ability to repair damage to the sarcolemma of muscle fibers. As a result, the damage accumulates and causes atrophy of the muscle fiber. It is unclear why this damage results in the specific pattern of weakness and characteristic atrophy Miyoshi myopathy. It is believed that Miyoshi myopathy is a variant of muscular dystrophy girdle rather than an independent alteration, because they are caused by mutations in the same gene and have signs and symptoms overlap.
The Year5 gene (anoctamin 5), located on the short arm of chromosome 11 (11p14.3), encoding anoctamina-5 protein. This protein is located within the endoplasmic reticulum membrane, involved in coding, processing and transport of proteins. It is believed that this protein acts as a channel, allowing chloride ions to flow into the interior and exterior of the endoplasmic reticulum. Flow regulation chloride within muscle cells plays a role in controlling muscle contraction and relaxation. The anoctamina-5 protein is also found in other cells, including cardiac muscle cells and bone cells. In addition, it is believed that anoctamina-5 protein may be important for the development of muscles and bones before birth.
They have identified at least 10 mutations in the gene Year5 in people with Miyoshi myopathy. Mutations in the gene change in the amino acid anoctamina-5 protein, resulting in little or synthesis of an abnormally short protein decomposes quickly, or inhibit the synthesis of anoctamina-5 protein. The effects of loss anoctamina-5 are also unclear. While chloride is necessary for normal muscle function, it is not clear how the lack of this chloride channel leads to the signs and symptoms of Miyoshi myopathy. The 191dupA mutation that can cause muscular dystrophy girdle, is also a frequent reason for Miyoshi myopathy in people of northern European descent. It is not known why 191dupA mutation can lead to different patterns of signs and symptoms. Miyoshi myopathy due to mutations in the gene is probably a Year5 variation girdle muscular dystrophy since it is due to mutations in the same gene , and in some cases even the same mutation.
This disease is inherited in an autosomal recessive pattern, that is, 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.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Miyoshi myopathy, by complete PCR amplification of the exons of the genes DYSF and Year5, respectively, 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).