KIF5A mutations cause an infantile onset phenotype including severe myoclonus with evidence of mitochondrial dysfunction

Ann Neurol. 2016 Oct;80(4):633-7. doi: 10.1002/ana.24744. Epub 2016 Aug 24.

Abstract

Missense mutations in kinesin family member 5A (KIF5A) cause spastic paraplegia 10. We report on 2 patients with de novo stop-loss frameshift variants in KIF5A resulting in a novel phenotype that includes severe infantile onset myoclonus, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest. We propose that alteration and elongation of the carboxy-terminus of the protein has a dominant-negative effect, causing mitochondrial dysfunction in the setting of an abnormal kinesin "motor." These results highlight the role of expanded testing and whole-exome sequencing in critically ill infants and emphasize the importance of accurate test interpretation. Ann Neurol 2016;80:633-637.

Publication types

  • Case Reports

MeSH terms

  • Apnea / genetics
  • Child, Preschool
  • Deglutition Disorders / genetics
  • Developmental Disabilities / genetics
  • Fatal Outcome
  • Female
  • Frameshift Mutation
  • Humans
  • Infant
  • Kinesin / genetics*
  • Male
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / genetics*
  • Muscle Hypotonia / genetics
  • Mutation
  • Myoclonus / genetics*
  • Optic Nerve / abnormalities

Substances

  • KIF5A protein, human
  • Kinesin