Clinical application of whole-exome sequencing: a novel autosomal recessive spastic ataxia of Charlevoix-Saguenay sequence variation in a child with ataxia.

IMPORTANCE Ataxia in children is a diagnostic challenge. Besides the more common acquired causes of ataxia, there are more than 50 inherited disorders associated with ataxia. Our objective was to highlight whole-exome sequencing as a rapidly evolving clinical tool for diagnosis of mendelian disorders, and we illustrate this in the report of a single case of a novel sequence variation in the SACS gene. OBSERVATIONS A 4-year-old girl presented with delayed gross motor development, ataxia, and polyneuropathy. Results of initial testing for the common causes of inherited and acquired ataxia were unrevealing. Whole-exome sequencing showed a novel frameshift homozygous sequence variation in the SACS gene, consistent with the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. CONCLUSIONS Whole-exome sequencing is a powerful clinical tool that has been increasingly used to assist in the diagnosis of mendelian disorders. It provides a cost-effective, efficient, and expedited approach to making a clinical diagnosis and, in some cases, may be the only way to make a diagnosis.