Spinocerebellar ataxia type 6 (SCA6) (Spinocerebellar ataxia type 6) - Gen CACNA1A.

Spinocerebellar ataxia type 6 (SCA6) is a disorder characterized by progressive movement problems. Initially, affected individuals manifest problems with coordination and balance. Other associated signs and symptoms include slurred speech, double vision and nystagmus. Over time, these individuals may develop loss of coordination in his arms, tremors and dystonia. Signs and symptoms of SCA6 usually start around 40 or 50 years old, but may appear at any time from childhood to late adulthood. Eventually, most of those affected require wheelchair assistance.

This process is due to mutations in CACNA1A, located on the short arm of chromosome 19 (19p13). This gene encodes a part (alpha1 subunit) of a calcium channel Cav2.1 called. This subunit forms the hole through which calcium ions can flow. These channels, transport of calcium ions across cell membranes and plays a key role in the ability of a cell to generate and transmit electrical signals. Calcium ions are involved in various cellular functions including cell-cell communication, muscle contraction, and regulation of certain genes. It is believed that Cav2.1 channels are also implicated in the survival of neurons and the ability of these cells to change and adapt over time.

The CACNA1A genetic mutations causing spinocerebellar ataxia type 6 (SCA6) involve a DNA segment known as a trinucleotide CAG repeat. Typically, the segment of CAG repeats 4 to 18 times within the gene. In people with SCA6, the CAG repeat segment is 20 to 33 times. People with 20 repetitions tend to exhibit signs and symptoms of SCA6 from late adulthood, while people with a greater number of repetitions usually have signs and symptoms since mid-adulthood. An increase in the length of the segment results CAG encoding an abnormally long version of the alpha-1 subunit. This version of the subunit alters the location and function of Cav2.1 channels. Typically, the alpha-1 subunit is within the cell membrane; subunits are anomalous in the cell membrane and into the cytoplasm, where they are grouped and form aggregates. Although the effect that these aggregates have in operation of the cell is unknown, the absence of normal calcium channels in the cell membrane affects cellular communication between neurons in the brain. A decrease in cell communication causes cell death. The cells within the cerebellum, are particularly sensitive to the accumulation of these aggregates. Eventually, a loss of cells in the cerebellum leads to problems characteristic SCA6 movement.

This disease is inherited as 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 spinocerebellar ataxia type 6 (SCA6), by complete PCR amplification of exons CACNA1A, 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).