title: ALS2 mutations: juvenile amyotrophic lateral sclerosis and generalized dystonia.
abstract: OBJECTIVE
  To determine the genetic etiology in 2 consanguineous families who presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral sclerosis associated with generalized dystonia.
  
  
  METHODS
  A combination of homozygosity mapping and whole-exome sequencing in the first family and Sanger sequencing of candidate genes in the second family were used.
  
  
  RESULTS
  Both families were found to have homozygous loss-of-function mutations in the amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene.
  
  
  CONCLUSIONS
  We report generalized dystonia and cerebellar signs in association with ALS2-related disease. We suggest that the ALS2 gene should be screened for mutations in patients who present with a similar phenotype.
authors.affiliation: From the Department of Molecular Neuroscience (U.-M.S.) and Sobell Department of Motor Neuroscience and Movement Disorders (M.S., K.P.B.), UCL Institute of Neurology, London, UK; University of Kiel (S.A.S., G.D., F.H.), Movement Disorders Clinic, Germany; Department of Paediatrics (L.C.), Great Ormond Street Hospital, London, UK; Second Department of Neurology (M.S.), University of Athens, Greece; and UCL Department of Molecular Neuroscience and UCL Genetics Institute (N.W.W.), University College London, UK.
authors.forename: Una-Marie
authors.initials: UM
authors.lastname: Sheerin
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
authors.forename: Lucinda
authors.initials: L
authors.lastname: Carr
authors.forename: Guenther
authors.initials: G
authors.lastname: Deuschl
authors.forename: Franziska
authors.initials: F
authors.lastname: Hopfner
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D003241:Consanguinity; D020821:Dystonic Disorders / Q000235:genetics*; D059472:Exome; D005260:Female; D005808:Genes, Recessive; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D017421:Sequence Analysis
chemical_list: C438187:ALS2 protein, human; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; C520412:SPG11 protein, human; C528699:ZFYVE26 protein, human