Frontotemporal dementia related granulin (GRN) (GRN-related frontotemporal dementia) - Gen GRN.            

Frontotemporal dementia associated with GRN is a progressive brain process that affects behavior, language and movement. Symptoms of the disease usually occur in the 50s or 60s and affected generally live 6 or 7 years after symptoms begin, although there are significant even in people of the same family variations.

Behavioral changes are the first symptoms of this type of dementia, and include personality changes, judgment and discernment, making it difficult for those affected the right deal with others. Sufferers are easily distracted and not complete missions, increasingly need more help in personal care and other daily activities. Many have impairment of speech and language, and may have difficulty speaking, remember words and names (Dysnomia). Over time, they can completely lose the ability to communicate. Some affected individuals may have problems with movement, such as Parkinsonism and corticobasal syndrome. Signs and symptoms of these conditions include stiffness, bradykinesia, myoclonus, dystonia, apraxia.

This process is the result of mutations in the gene GRN (granulin), located on the long arm of chromosome 17 (17q21.32), encoding the "granulin" protein (progranulin). Granulin is active in many body tissues, but is more active in cells that divide rapidly, such as skin cells and the gastrointestinal mucosa, participating in growth control, cell division and survival. It also plays an important role in early embryonic development, regulation of immune response and wound healing. Granulin function in the brain is not well understood, although it seems that intervene in the survival of neurons.

There are more than 65 GRN mutations in the gene in people affected by this type of dementia. The most frequent mutation is Arg493Ter (R493X) which causes a premature termination in the synthesis of the protein. Most mutations in this gene would prevent granulin be coded from one of the gene copies. As a result, the cell would produce only half of the usual amount of granulin. Some studies have shown that this involvement is characterized by the development of a protein called TAR DNA-binding protein (TDP-43) in some neurons. TDP-43 aggregates form that can interfere with cell function and eventually lead to cell death protein. It is investigated the interrelation between granulin deficiency and intracellular accumulation of the TDP-43 protein. In affected there is a gradual loss of neurons in the frontal and temporal lobes of the brain. The frontal lobe is involved in reasoning, planning, judgment and problem solving, while the temporal lobe is involved in hearing, speech, memory and emotions. Death of neurons in these areas leads to problems that manifest these patients. However, it is not clear why the affected persons of this type of dementia, loss of neurons occurs in the frontal and temporal lobes more frequently than in other brain regions.

This process is inherited as an autosomal dominant, which means that an altered copy of the gene in each cell is sufficient to cause the process. In most cases, an affected have a parent or other family members with the process.

Tests in IVAMI: in IVAMI perform detection of mutations associated with frontotemporal dementia associated with GRN, by complete PCR amplification of the exons of the gene GRN, 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).