Liddle syndrome ... (Liddle syndrome) - Genes SCNN1B and SCNN1G
Liddle syndrome is a rare condition characterized by hypertension. Besides hypertension, affected patients may have metabolic alkalosis, hypokalemia or hypokalemia, low concentrations of aldosterone activity and suppression of plasma renin.
This may be due to mutations in genes SCNN1B, located on the short arm of chromosome 16 (16p12.2-P12.1) or SCNN1G, located on the short arm of chromosome 16 (16p12). Each of these genes encodes a subunit (gamma subunit and beta subunit, respectively) of the epithelial sodium channel (ENaC). These channels are in the surface of epithelial cells in many tissues of the body, including the kidneys, where sodium channels carry cells. In the kidney, ENaC opens in response to signals sodium concentrations in blood when they are too low, allowing sodium to flow into the cells. From kidney cells, sodium is reabsorbed into the blood stream instead of being eliminated from the body through urine. In addition to regulating the amount of sodium in the body, the flow of sodium ions helps control the movement of water in the tissues. For example, ENaC channels in lung cells help to regulate the amount of fluid in the lungs.
In those affected by Liddle syndrome they have identified at least 16 mutations in the gene SCNN1B to 5 mutations in the gene SCNN1G. These genetic changes result encoding a beta subunit or gamma abnormally short or substitute a single amino acid in the protein. These changes affect an important region of the protein involved in signaling its degradation. As a result, the proteins are not degraded, and remain more ENaC channels on the cell surface. Increasing the channels on the cell surface increases abnormally sodium reabsorption (followed by water), causing hypertension. Sodium reabsorption in blood is related to the removal of blood potassium, so excess sodium reabsorption causes hypokalemia.
Individuals affected by this disease unresponsive to treatment with spironolactone drug commonly used as a potassium - sparing diuretic and therefore used in patients with hypertension with low renin levels and hypokalemia. Genetic analysis is therefore recommended in hypertensive patients with low renin levels that do not respond to treatment with spironolactone.
Liddle syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the process to be expressed.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Liddle syndrome, by complete PCR amplification of the exons of SCNN1B and SCNN1G, 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).