Spinocerebellar ataxia type 1 (Spinocerebellar ataxia type 1 -SCA1-) - Gen ATXN1

Spinocerebellar ataxia type 1 (SCA1: Spinocerebellar Ataxia type 1), is a process characterized by progressive movement problems affecting motor coordination and balance (ataxia). Other signs include impairment of speech and swallowing, spasticity, and ophthalmoplegia. The weakness of ocular muscles causes nystagmus. Patients may have difficulty processing, learn and remember information (cognitive impairment). Eventually, individuals with SCA1 can develop sensory neuropathy, dystonia, muscle wasting (atrophy) and twitches. Rarely it has been reported stiffness, tremors and jerky involuntary movements (chorea) in people who have been affected for many years.

Signs and symptoms of the disorder usually manifest in early adulthood, but can occur at any time from childhood to late adulthood. People with SCA1 typically survive 10 to 20 years after the onset of symptoms.

The mutations in the affected ATXN1 gene located on the short arm of chromosome 6 (6p23). This gene contains the information for the synthesis of the "ataxin-1" protein. This protein is found in the cell nucleus throughout the body, but its function is unknown. It is thought that the "ataxin-1" can participate in the regulation of protein synthesis, including the early stages of protein production (transcription), and processing of the messenger RNA.

ATXN1 gene mutations affect a part of the DNA sequence of chromosome 6 with repetitions CAG. Normally, the sequence CAG, has of 4-39 repetitions. In affected by SCA1, this triplet is repeated between 40 and 80 times. Those affected with 40 to 50 CAG repeats develop the first signs and symptoms in middle age of life; while those with more than 70 repetitions, they develop signs and symptoms in adolescence. The increase in length of the sequence CAG repeats, resulting in a protein "ataxin-1" excessively long, which is folded in a wrong three - dimensional structure. This abnormal protein binds to other proteins to form aggregates in the nucleus of cells. These aggregates prevent the "ataxin-1" operates normally, damaging cells and causing their death. For unknown reasons, aggregates "ataxin-1", only found in the brain and spinal cord (CNS). The cells of the cerebellum, responsible for controlling the movements are very sensitive to changes in form and function "ataxin-1".

The disease has an autosomal dominant, which means that a single copy of the gene altered in each cell is sufficient to trigger the disease. An affected person inherits the altered gene from one affected parent, although some affected do not have a parent with the disease. When moving from one generation to the next, the length of the sequence triplet CAG repeated often increases, and repeats often associated with earlier onset of signs and symptoms (early), which in turn is more evident when the gene is inherited from the father altered. People with about 35 repetitions of CAG do not develop the disease but are at risk of their offspring developing affectation, since moving from parent to child, the size of the repeated sequences increases.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated conataxia spinocerebellar type 1 (SCA1), by complete PCR amplification of exons ATXN1 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).