ALS2 mutations: juvenile amyotrophic lateral sclerosis and generalized dystonia

Neurology. 2014 Mar 25;82(12):1065-7. doi: 10.1212/WNL.0000000000000254. Epub 2014 Feb 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Carrier Proteins / genetics
  • Child
  • Consanguinity
  • Dystonic Disorders / genetics*
  • Exome
  • Female
  • Genes, Recessive
  • Guanine Nucleotide Exchange Factors / genetics*
  • Homozygote
  • Humans
  • Male
  • Mutation / genetics
  • Pedigree
  • Phenotype
  • Proteins / genetics
  • Sequence Analysis


  • ALS2 protein, human
  • Carrier Proteins
  • Guanine Nucleotide Exchange Factors
  • Proteins
  • SPG11 protein, human
  • ZFYVE26 protein, human

Supplementary concepts

  • Amyotrophic Lateral Sclerosis 2, Juvenile