This gene consists of nine exons including a gigantic exon spanning more than 12.8k bp. It encodes the sacsin protein, which includes a UBQ region at the N-terminus, a HEPN domain at the C-terminus and a DnaJ region upstream of the HEPN domain. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy.
Autosomal Recessive Spastic Ataxia of the Charlevoix-Saguenay (ARSACS) is a hereditary progressive neurological disorder that primarily affects people from the Saguenay–Lac-Saint-Jean and Charlevoix regions of Quebec or descendants of native settlers in this region. It is characterized by degeneration of the spinal cord and progressive damage of the peripheral nerves. The disorder is caused by a gene mutation on chromosome 13 (SACS) of the 22 chromosomes that determine characteristics that are not related to sex. This is an autosomal recessive disorder, meaning that both parents must be carriers of the gene in order to have a 25% chance of their child having the disorder at each pregnancy. Mutations of the gene is usually a deletion or replacement of a nucleotide in the SACS gene. The mutation of the SACS gene causes the production of an unstable, poorly functioning SACSIN protein. It is unclear as to how this mutation affects the central nervous system (CNS) and skeletal muscles presenting in the signs and symptoms of ARSACS.
ARSACS is usually diagnosed in early childhood, approximately 12–24 months of age when a child begins to take their first steps. It is a lack of coordination and balance during gait that is first noticed. Children with the disorder take frequent falls and appear to have an unsteady (Ataxic) gait. Some of the signs and symptoms include: Stiffness of the legs, appendicular and trunk ataxia, hollow foot and hand deformities, ataxic dysarthria, distal muscle wasting, horizontal gaze nystagmus, and spasticity.
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