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

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

Author information

1
McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD. jduis1@jhmi.edu.
2
Pediatric Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
3
McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
4
Carolinas Pediatric Neurology Care, Charlotte, NC.
5
Department of Molecular and Human Genetics, Baylor Miraca Genetics Laboratories, Baylor College of Medicine, Houston, TX.
6
Carolinas Pathology Group, Charlotte, NC.
7
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.

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.

PMID:
27463701
PMCID:
PMC5042851
DOI:
10.1002/ana.24744
[Indexed for MEDLINE]
Free PMC Article

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