Proteus syndrome (Proteus syndrome) - Gen AKT1.
Proteus syndrome is a rare disease characterized by excessive bone growth, skin and other tissues. Organs and tissues affected by the disease grow disproportionately compared to the rest of the body. This overgrowth is often asymmetrical, affecting the right and left sides of the body differently. Newborns with Proteus syndrome have few or no signs of the disease. Overgrowth is evident between the ages of 6 and 18 months and becomes more intense with age.
In people with Proteus syndrome, excessive growth pattern varies greatly but can affect almost any part of the body. Often, the disease affects the limb bones, skull and spine. This disease can also cause a variety of skin growths, especially dense, elevated lesion, and very grooved connective tissue known as cerebriform nevus. In addition, the vascular tissue and adipose tissue may also grow abnormally in affected individuals. Some people have neurological abnormalities, including mental retardation, seizures and vision loss. Affected individuals may also have distinctive facial features as an elongated face, outer ends of the eyes directed down a low nasal bridge, wide nostrils, and an expression with his mouth open. For reasons that are not clear, people affected with neurological symptoms are more likely to have characteristic neurological symptoms than those without facial features. It is unclear how these signs and symptoms are related to abnormal growth.
Other potential complications of Proteus syndrome include a higher risk of developing several types of benign tumors and deep vein thrombosis (DVT). DVT occurs most commonly in the deep veins of the legs or arms. If these clots travel through the bloodstream, they can reach the lungs and cause pulmonary embolism. Pulmonary embolism is a common cause of death in people with Proteus syndrome.
Proteus syndrome is due to mutations in the gene AKT1, located on the long arm of chromosome 14 (14q32.32). This gene encodes a protein called kinase AKT1. This protein is found in various cell types throughout the body, where it plays a critical role in many signaling pathways. For example, the kinase AKT1 helps regulate the growth, proliferation, differentiation and cell survival. Furthermore, this protein helps regulate apoptosis. Kinase signaling involving AKT1 appears to be essential for normal development and function of the nervous system. It is likely to play a role in cell to cell communication between neurons, neuronal survival and memory formation. The AKT1 gene belongs to a class of genes known as oncogenes. When they suffer a mutation, oncogenes have the potential to cause normal cells to become cancerous.
It has identified at least one mutation in AKT1 gene in people with Proteus syndrome. This mutation changes a single amino acid in kinase AKT1. Specifically, the amino acid glutamic acid is replaced by the amino acid lysine at position 17 protein (E17K Glu17Lys or). The Glu17Lys coding mutation leads to an overactive kinase AKT1 alters the ability of a cell to regulate their own growth, allowing the cell to grow and divide abnormally. Increasing cell proliferation in various tissues and organs leads to overgrowth feature Proteus syndrome. Studies suggest that mutation of AKT1 gene is more common in groups of cells overgrowths in parts of the body which normally grow.
Proteus syndrome is due to AKT1 gene mutations that occur in early development, so the disease is not hereditary.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Proteus syndrome by complete PCR amplification of AKT1 gene exons 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).