Frontotemporal dementia related CHMP2B (frontotemporal dementia-related CHMP2B) - Gen CHMP2B
Frontotemporal dementia is related to CHMP2B progressive brain process that affects personality, behavior and language. Symptoms of the disease are usually evident between 50 and 60 years of age, and affected individuals survive about 3 to 21 years after the onset of symptoms.
The first most common signs are changes in personality and behavior. These changes include inappropriate emotional responses, restlessness, loss of initiative and neglect of personal hygiene. In addition, affected individuals may overeat sweet foods or non - food items placed in his mouth (hyperorality), develop aphasia, dyscalculia and problems with movement. These abnormal movements include stiffness, tremors, dystonia and myoclonus. As the disease progresses, the most affected people become unable to walk.
This process is due to alterations in the gene sequence CHMP2B (multivesicular body charged protein 2B), located on the short arm of chromosome 3 (3p11.2), which encodes a protein found in the brain, which appears to be essential for the survival of neurons. This protein is a subunit of a group of proteins known as the ESCRT-III complex. This complex helps carry other membrane proteins into the cell, a process known as endocytosis. In particular, the ESCRT-III complex is involved in the endocytosis of proteins that need to be degraded by the cell. The complex helps to sort these proteins in multivesicular bodies (MVBs), which incorporate the lysosomes. The CHMP2B protein is regulated by a segment at one end of the protein known as the C-terminal domain. This domain usually keeps the inactive protein. The inactive protein is incapable of interacting with other subunits of ESCRT-III complex, which prevents formation of the complex when it is not needed. The C-terminal domain also plays an important role in dismantling the ESCRT-III complex through interaction with the vacuolar protein sorting 4 (Vps4).
Although changes are considered rare in the gene responsible CHMP2B frontotemporal dementia, at least two of these genetic changes are thought to be the disease - causing mutations. It is unclear whether other genetic changes can also cause disease, because they can be rare variations that are not related to the development of frontotemporal dementia. Most people with frontotemporal dementia related to CHMP2B are members of the same family of Danish origin. Affected individuals in this family have a particular mutation, 532-1G> C, resulting in two abnormal encoding CHMP2B versions of the protein which is absent the C-terminal domain at one end. Without this segment, the protein is constantly active, which interrupts the transport and degradation of other proteins. Ultimately, these abnormalities cause the death of neurons in the brain, particularly in regions near the frontal and temporal lobes.
Frontotemporal dementia related CHMP2B is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person has a parent with the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with frontotemporal dementia related CHMP2B by the complete PCR amplification of exons CHMP2B 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).