title: Clinical application of whole-exome sequencing: a novel autosomal recessive spastic ataxia of Charlevoix-Saguenay sequence variation in a child with ataxia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA
authors.forename: Wendy K M
authors.initials: WK
authors.lastname: Liew
authors.forename: Tawfeg
authors.initials: T
authors.lastname: Ben-Omran
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Prabhu
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Matteo
authors.initials: M
authors.lastname: Vatta
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
mesh_terms: D002675:Child, Preschool; D059472:Exome / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D009128:Muscle Spasticity / Q000175:diagnosis* / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D020754:Spinocerebellar Ataxias / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics