title: Novel SACS mutations identified by whole exome sequencing in a norwegian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.
abstract: We employed whole exome sequencing to investigate three Norwegian siblings with an autosomal recessive spastic ataxia and epilepsy. All patients were compound heterozygous (c.13352T>C, p.Leu4451Pro; c.6890T>G, p.Leu2297Trp) for mutations in the SACS gene establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The clinical features shown by our patients were typical of this disorder with the exception of epilepsy, which is a rare manifestation. This is the first report of ARSACS in Scandinavian patients and our findings expand the genetic and clinical spectrum of this rare disorder. Moreover, we show that exome sequencing is a powerful and cost-effective tool for the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.
authors.affiliation: Department of Neurology, Haukeland University Hospital, Bergen, Norway ; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Tzoulis
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.forename: Bjørn Ivar
authors.initials: BI
authors.lastname: Haukanes
authors.forename: Helge
authors.initials: H
authors.lastname: Boman
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Knappskog
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Bindoff
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001921:Brain / Q000473:pathology; D059472:Exome; D005190:Family; D005260:Female; D005808:Genes, Recessive; D006360:Heat-Shock Proteins / Q000235:genetics*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009128:Muscle Spasticity / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009664:Norway; D016415:Sequence Alignment; D020754:Spinocerebellar Ataxias / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human