Recessive mutations in the SACS gene cause a neurological disorder called Autosomal Recessive Ataxia of Charlevoix-Saguenay. Disease onset is typically in early childhood and progression consists in delayed acquisition of motor milestones, in particular, walking due to unsteadiness in toddlers, followed by lower-limb spasticity and peripheral neuropathy. Onset has also been observed in childhood or adolescence. Other clinical symptoms like ocular disturbances, dysarthria, and upper-limb ataxia develop at a slower rate. Finally, mild intellectual disability, hearing loss, and incontinence have also been documented in some individuals.
Genetics testing shows that ARSACS is more frequent than thought and mutations in SACS is the second cause of ataxia. Because ARSACS is an autosomal recessive disorder, it is believed that ARSACS is caused by loss-of-function mutations of the SACS gene reflected by the absence of expression of the 520kDa-giant protein sacsin.
SACS