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

Jessica Duis, Shannon Dean, Carolyn Applegate, Amy Harper, Rui Xiao, Weimin He, James D. Dollar, Lisa Sun, Marta Biderman Waberski, Thomas Owen Crawford, Ada Hamosh, Carl Stafstrom

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAnnals of Neurology
DOIs
StateAccepted/In press - 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Neurology
  • Clinical Neurology

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