Homozygous mutation of VPS16 gene is responsible for an autosomal recessive adolescent-onset primary dystonia

Sci Rep. 2016 May 12;6:25834. doi: 10.1038/srep25834.


Dystonia is a neurological movement disorder that is clinically and genetically heterogeneous. Herein, we report the identification a novel homozygous missense mutation, c.156 C > A in VPS16, co-segregating with disease status in a Chinese consanguineous family with adolescent-onset primary dystonia by whole exome sequencing and homozygosity mapping. To assess the biological role of c.156 C > A homozygous mutation of VPS16, we generated mice with targeted mutation site of Vps16 through CRISPR-Cas9 genome-editing approach. Vps16 c.156 C > A homozygous mutant mice exhibited significantly impaired motor function, suggesting that VPS16 is a new causative gene for adolescent-onset primary dystonia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Animals
  • Base Sequence
  • CRISPR-Cas Systems / genetics
  • Child
  • Chromosomes, Human, Pair 20 / genetics
  • Conserved Sequence / genetics
  • DNA Mutational Analysis
  • Dystonic Disorders / genetics*
  • Female
  • Gene Editing
  • Genes, Recessive*
  • Genetic Testing
  • Homozygote
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Mutation / genetics*
  • Mutation, Missense / genetics
  • Pedigree
  • Phenotype
  • Vesicular Transport Proteins / genetics*
  • Whole Exome Sequencing


  • VPS16 protein, human
  • Vesicular Transport Proteins