A Novel Homozygous SACS Mutation Identified by Whole-Exome Sequencing in a Consanguineous Family with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a hereditary neurological disorder mostly manifested with a classical triad: progressive early-onset cerebellar ataxia, lower limb pyramidal signs, and peripheral neuropathy. We employed whole-exome sequencing and bioinformatics to identify the genetic cause in an ARSACS patient from a consanguineous family. Based on whole-exome sequences of the patient and her healthy parents, a novel homozygous deletion variant (NM_014363: c.9495_9508del; p.F3166Tfs*9) in the SACS gene was identified in the patient. This frameshift mutation is predicted to generate a truncated sacsin protein, which results in the loss of the C-terminal 1,406 amino acids. Our study provides a potential genetic diagnosis for the patient and expands the spectrum of SACS mutations.