title: Exome sequencing: an efficient diagnostic tool for complex neurodegenerative disorders.
abstract: OBJECTIVE
  Autosomal recessive cerebellar ataxia (ARCA) comprises a large and heterogeneous group of neurodegenerative disorders. We studied three families diagnosed with ARCA.
  
  
  METHODS
  To determine the gene lesions responsible for their disorders, we performed high-density single-nucleotide polymorphism genotyping and exome sequencing.
  
  
  RESULTS
  We identified a new mutation in the SACS gene and a known mutation in SPG11. Notably, we also identified a homozygous variant in APOB, a gene previously associated with ataxia.
  
  
  CONCLUSIONS
  These findings demonstrate that exome sequencing is an efficient and direct diagnostic tool for identifying the causes of complex and genetically heterogeneous neurodegenerative diseases, early-stage disease or cases with limited clinical data.
authors.affiliation: Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia.|Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Hammer
authors.affiliation: Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia.
authors.forename: G
authors.initials: G
authors.lastname: Eleuch-Fayache
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.|Reta Lilla Weston Laboratories and Departments of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Gibbs
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Arepalli
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Chong
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.|Reta Lilla Weston Laboratories and Departments of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Sassi
authors.affiliation: Institute of Human Genetics, UCSF, San Francisco, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Bouhlal
authors.affiliation: Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia.
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.affiliation: Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia.
authors.forename: R
authors.initials: R
authors.lastname: Amouri
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D059472:Exome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D006360:Heat-Shock Proteins; D011506:Proteins; C404403:SACS protein, human; C520412:SPG11 protein, human