Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia

Neurology. 2016 Jul 5;87(1):65-70. doi: 10.1212/WNL.0000000000002813. Epub 2016 Jun 8.

Abstract

Objective: To describe the phenotypes in 2 families with vaccinia-related kinase 1 (VRK1) mutations including one novel VRK1 mutation.

Methods: VRK1 mutations were found by whole exome sequencing in patients presenting with motor neuron disorders.

Results: We identified pathogenic mutations in the VRK1 gene in the affected members of 2 families. In family 1, compound heterozygous mutations were identified in VRK1, c.356A>G; p.H119R, and c.1072C>T; p.R358*, in 2 siblings with adult onset distal spinal muscular atrophy (SMA). In family 2, a novel VRK1 mutation, c.403G>A; p.G135R and c.583T>G; p.L195V, were identified in a child with motor neuron disease.

Conclusions: VRK1 mutations can produce adult-onset SMA and motor neuron disease in children without pontocerebellar hypoplasia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Child, Preschool
  • Family
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Motor Neuron Disease / diagnosis
  • Motor Neuron Disease / genetics*
  • Motor Neuron Disease / pathology
  • Motor Neuron Disease / physiopathology*
  • Mutation*
  • Pedigree
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • VRK1 protein, human