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

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

Ann Neurol. 2016 Jul 27;

Authors: Duis J, Dean S, Applegate C, Harper A, Xiao R, He W, Dollar JD, Sun LR, Biderman Waberski M, Crawford TO, Hamosh A, Stafstrom CE

Abstract
Missense mutations in kinesin family member 5A (KIF5A) cause spastic paraplegia 10. We report two 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. This article is protected by copyright. All rights reserved.

PMID: 27463701 [PubMed - as supplied by publisher]

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