Spastic Ataxia Charlevoix-Saguenay (Spastic ataxia of Charlevoix-Saguenay -ARSACS-) - Gen SACS

Spastic ataxia of Charlevoix the Saguenay-autosomal recessive (ARSACS: Spastic Ataxia Autosomal Recessive of Charlevoix-Saguenay) is a neurodegenerative disease named after having initially described in regions of Charlevoix and Saguenay-Lac St. Jean Northeast Quebec (Canada ) affecting Canadians of French origin who live in these regions. Subsequently it described worldwide.

This disease is characterized by spastic ataxia early onset in infancy with peripheral neuropathy with or without mental retardation, sometimes with dysarthria, nystagmus, hypomyelination retinal distal muscle weakness, amyotrophy, dysarthria or deformities of fingers and toes. It found some cases associated with deafness and mitral valve prolapse. Affected patients suffer from a defect of myelination of the central and peripheral nervous system. The progressive axonal degeneration in the corticospinal tract and spinocerebellar lead to peripheral clinical signs.

The genetic basis of this disease resides in the SACS gene (Spastic Ataxia Charlevoix-Saguenay) located on the long arm of chromosome 13 (13q12). This gene encodes a protein called sacsina, located in the brain, skin cells, skeletal muscle, and in low levels in pancreas. Although the exact function is unknown sacsina protein is believed to play a role in could folding of proteins in the appropriate three - dimensional shape because it shares similar regions with other proteins that perform this function.

They have identified at least 30 SACS gene mutations in people with spastic ataxia of Charlevoix-Saguenay autosomal recessive (ARSACS). Most mutations in the SACS gene deleted either one or more nucleotides or replace one nucleotide for another nucleotide in SACS gene, resulting in the coding of a sacsina malfunctioning. They described two common mutations in people suffering from Quebec. One of these mutations deletes the thymine nucleotide at position 6594 in the SACS gene (6594delT). This mutation is found in over 90% of people with ARSACS in Quebec. The other mutation replaces thymine cytosine nucleotide by nucleotide at position 5254 in the SACS gene (C5254T). Both mutations result sacsina coding a protein that is abnormally short, nonfunctional. It is unclear how the abnormal protein sacsina affects the brain muscles and skeleton, causing signs and symptoms associated with ARSACS.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated spastic Charlevoix-Saguenay conataxia autosomal recessive, by complete PCR amplification of exons SACS 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).