Progressive supranuclear palsy (Progressive supranuclear palsy) - Gen MAPT


Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech and cognition. Signs and symptoms of this condition usually become evident in mid to late adulthood, most often in the 60s of a person. Most of those affected survive five to nine years after first manifest the disease, although some affected individuals have lived for more than a decade.

Early signs and symptoms of the disease often include loss of balance and frequent falls and walking problems, including poor coordination and staggering gait unsteady. Other abnormal movements develop as the disease progresses, including unusually slow movements (bradykinesia), awkwardness and rigidity of muscles of the trunk. These problems are compounded over time and, ultimately, the most affected people require a wheelchair. Another characteristic sign is the abnormal eye movement. Paralysis of vertical gaze is a characteristic of this disease. Other problems include difficulty eye movements to open and close the eyelids, frequent blinking and reverse eyelids. These abnormalities can cause blurred vision, photophobia, and a stare. Additional features include dysarthria and dysphagia. Most affected individuals also experience changes in personality and behavior, such as apathy. They develop cognitive problems, including difficulties with attention, planning and problem solving. As cognitive and behavioral problems worsen, people affected increasingly require assistance with personal care and other activities of daily living.

In most cases, the genetic cause of the disease is unknown. In rare cases, the disease is due to mutations in the MAPT gene (microtubule associated tau protein), located on the long arm of chromosome 17 (17q21.1). This gene encodes a protein called tau, which is found throughout the nervous system, including neurons. This protein is involved in the assembly and stabilization of microtubules, which are rigid, hollow fibers that make up the cytoskeleton. Microtubules help cells to maintain their shape, help in the process of cell division and are essential for transporting material within cells. Six different isoforms of tau protein occurring in the adult brain. Isoforms vary in length from 352 to 441 amino acids. A region of a protein called the microtubule binding domain, also varies between isoforms. In three of the isoforms, the domain of microtubule binding contains three repeated segments. In the other three isoforms, this domain contains four repeated segments. Generally, the brain has approximately the same amount of isoforms with three repeated segments and four repeating segments. This balance seems to be essential for normal function of neurons.

Several mutations have been identified in the MAPT gene in people with progressive supranuclear palsy. However, mutations in this gene appear to be a rare cause of this disease. At least one polymorphism in the MAPT gene has been associated with an increased risk of developing progressive supranuclear palsy. This polymorphism, known as the H1 haplotype, is much more frequently in people with progressive supranuclear palsy than in the general population. It is unclear exactly how this genetic variation increases the risk of developing this disease. MAPT gene mutations alter the structure and normal function of tau protein. Defective protein assembles in abnormal accumulations inside neurons and other brain cells, although it is unclear what effect these groups in cellular function and survival, which results in the progressive death of brain cells, especially in the deep structures of the brain that are essential for the coordination of movement. This loss of brain cells underlying abnormal movements and other disease characteristics.

This disease is one of several related diseases known as tauopathies, which are characterized by an abnormal accumulation of tau in the brain. It is thought that other genetic and environmental factors also contribute to the progressive supranuclear palsy. For example, the disease has been associated with genetic changes in chromosome 1 and chromosome 11. However, have not been identified specific genes involved.

Most cases of progressive supranuclear palsy are sporadic, meaning that occur in people with no history of disease in your family. However, some people with the disorder have relatives with related parties , such as parkinsonism and dementia diseases. When the disease is hereditary, you can have an autosomal dominant inheritance, which means that a copy of an altered gene in each cell is sufficient to express the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with progressive supranuclear palsy, by complete PCR amplification of the exons of the MAPT 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).