Catecholaminergic polymorphic ventricular tachycardia (catecholaminergic polymorphic ventricular tachycardia) - Genes RYR2, CASQ2.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition characterized by cardiac arrhythmia. Heart rate increases in response to physical activity or emotional stress, which can trigger an abnormally rapid, irregular heart rhythm called ventricular tachycardia. Episodes of ventricular tachycardia can cause dizziness, dizziness and syncope. In people with CPVT, these episodes usually begin in childhood. If the condition is not recognized and untreated, an episode of ventricular tachycardia can cause cardiac arrest, leading to sudden death.
This process is due to mutations in genes RYR2 and CASQ2. These genes encode proteins that help maintain a regular heartbeat. For the heart to beat normally, myocytes must contract and relax in a coordinated manner. Both RYR2 as CASQ2 are involved in the management of calcium into muscle cells. Mutations in these genes disrupt the management of calcium into muscle cells. During exercise or emotional stress, impaired regulation of calcium in the heart can lead to ventricular tachycardia in people with CPVT.
The RyR2 located on the long arm of chromosome 1 (1q43), encoding the receptor protein ryanodine-2. They have identified more than 70 mutations in the gene that cause CPVT RYR2. Most of these mutations change protein amino ryanodine receptor-2, altering the structure and function of channel RYR2, interrupting the flow control of calcium ions in the myocytes, which can trigger an abnormal heart rhythm in people with CPVT.
The CASQ2 gene, located on the short arm of chromosome 1 (1p13.1), encoding calsequestrin-2 protein, which is found in the heart, where it participates in the storage and transport of calcium ions. Within myocytes calsequestrin-2 it is in the sarcoplasmic reticulum, which acts as a storage facility of calcium ions, by binding to calsequestrin-2. This protein also helps regulate a protein called channel RYR2, which controls the flow of calcium ions from the sarcoplasmic reticulum. The resulting increase in the concentration of calcium ions triggers the heart muscle, which pumps blood out of the heart. Next, calcium ions are transported back into the sarcoplasmic reticulum, and the heart muscle relaxes. Thus, the release and reuptake of calcium ions in the myocytes a regular heartbeat.
They have identified at least seven mutations in the gene in people with CASQ2 CPVT. Some of these mutations change encoding nucleotide calsequestrin-2 protein, while other mutations prevent the production of any functional calsequestrin-2. Impaired or absent protein is unable to perform their usual function in the binding of calcium within the myocytes. In addition to not function properly, calsequestrin-2 can also affect regulation RYR2 channel, causing loss of sarcoplasmic reticulum calcium ions. These changes alter the precise control of the flow of calcium ions in the myocytes, which can trigger an abnormal heart rhythm in people with CPVT.
When the disease results from mutations in the RyR2 has an autosomal dominant inheritance. Autosomal dominant inheritance means that a copy of the altered gene in each cell is sufficient to cause the disorder. In about half the cases, an affected person inherits a genetic mutation from an affected parent RYR2. The remaining cases result from new mutations in the gene RYR2 and occur in people with no history of disease in your family.
When the disease is caused by mutations in the gene CASQ2, the condition has an autosomal recessive inheritance 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 polymorphic ventricular tachycardia (CPVT), by complete PCR amplification of the exons of RYR2 and CASQ2, respectively, and subsequent sequencing genes.
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).