Autosomal recessive cerebellar ataxia type 1-ARCA1- (cerebellar ataxia Autosomal recessive type 1 -ARCA1-) - Gen SYNE1.
Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a disorder characterized by progressive movement problems due to atrophy of nerve cells in the cerebellum. Signs and symptoms of the disease first appear early and mid-adulthood. Initially, those affected have dysarthria, ataxia , or both. They may also have dismetría. Other features include nystagmus and problems in tracking the movements of objects with eyes. Movement problems progress slowly and often require a cane, walker or wheelchair.
This disease is due to mutations in the gene SYNE1, located on the long arm of chromosome 6 (6q25). This gene encodes a protein called Syne-1 found in many tissues, but appears to be particularly critical in the brain. Within the brain, Syne-1 protein appears to play a role in maintaining the cerebellum. The syne-1 protein is expressed in Purkinje cells, which are found in the cerebellum and are involved in chemical signaling between neurons.
Have identified at least seven mutations in the gene SYNE1 in individuals with autosomal recessive cerebellar ataxia type 1. All mutations have been identified create an early signal stop encoding Syne-1. These mutations result in an abnormally short and dysfunctional version Syne-1 protein. It is likely to affect the defective protein function Purkinje cells and disrupt signaling between neurons in the cerebellum. Loss of brain cells in the cerebellum causes movement problems characteristic of the disease, but it is unclear how this cell loss is related to the impaired function of Purkinje cells.
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 with autosomal recessive cerebellar ataxia type 1 (ARCA1), by complete PCR amplification of exons SYNE1 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).