Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia

J Neurol. 2014 Nov;261(11):2165-9. doi: 10.1007/s00415-014-7457-x. Epub 2014 Aug 23.


We describe two pairs of siblings from a consanguineous family manifesting autosomal recessive hereditary spastic paraplegia caused by a novel mutation in the EXOSC3 gene, previously reported in pontocerebellar hypoplasia type 1. Clinical findings included delayed motor milestones, early-onset spastic paraplegia, variable cognitive disability, and cerebellar signs. Cerebral imaging demonstrated enlarged cisterna magna and mild hypoplasia and atrophy of the lower vermis with a normal pons. Genetic analysis using homozygosity mapping followed by whole exome sequencing identified homozygous c.571G>T; p.G191C mutation in the EXOSC3 gene. We suggest that EXOSC3 mutations may present not only as pontocerebellar hypoplasia type 1, but also as a complicated form of hereditary spastic paraplegia without pontine hypoplasia or atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Child
  • Exosome Multienzyme Ribonuclease Complex / genetics*
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • RNA-Binding Proteins / genetics*
  • Spastic Paraplegia, Hereditary / diagnosis*
  • Spastic Paraplegia, Hereditary / genetics*
  • Young Adult


  • EXOSC3 protein, human
  • RNA-Binding Proteins
  • Exosome Multienzyme Ribonuclease Complex