title: Prominent sensorimotor neuropathy due to SACS mutations revealed by whole-exome sequencing.
abstract: OBJECTIVE
  To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings.
  
  
  METHODS
  Case reports and whole-exome DNA sequencing.
  
  
  METHODS
  Neurogenetics clinic, Institute of Genetic Medicine, Newcastle upon Tyne, England.
  
  
  METHODS
  Two adult siblings with a sensorimotor neuropathy, ataxia, and spasticity.
  
  
  METHODS
  Clinical, neurophysiological, imaging, and genetic data.
  
  
  RESULTS
  Novel compound heterozygous frameshift mutations were detected in the SACS gene of both siblings, predicted to drastically truncate the sacsin protein.
  
  
  CONCLUSIONS
  Whole-exome sequencing rapidly defined the genetic cause of the disorder, expanding the clinical phenotype associated with SACS mutations to include a severe sensorimotor neuropathy.
authors: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, England.
authors: Angela
authors: A
authors: Pyle
authors: Helen
authors: H
authors: Griffin
authors: Patrick
authors: P
authors: Yu-Wai-Man
authors: Jennifer
authors: J
authors: Duff
authors: Gail
authors: G
authors: Eglon
authors: Stuart
authors: S
authors: Pickering-Brown
authors: Mauro
authors: M
authors: Santibanez-Korev
authors: Rita
authors: R
authors: Horvath
authors: Patrick F
authors: PF
authors: Chinnery
mesh_terms: D000328:Adult; D059472:Exome / Q000235:genetics*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009128:Muscle Spasticity / Q000150:complications / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017422:Sequence Analysis, DNA; D035781:Siblings; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human