KIF5A mutations cause an infantile onset phenotype including severe myoclonus with evidence of mitochondrial dysfunction. Issue 4 (24th August 2016)

• Record Type: Journal Article
• Authors: Duis, Jessica; Dean, Shannon; Applegate, Carolyn; Harper, Amy; Xiao, Rui; He, Weimin; Dollar, James D.; Sun, Lisa R.; Waberski, Marta Biderman; Crawford, Thomas O.; Hamosh, Ada; Stafstrom, Carl E.
• Is Part Of: Annals of neurology. Volume 80:Issue 4(2016:Oct.)
• Page Start: 633
• Page End: 637
• Publication Date: 2016-08-24
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24744
• Languages: English
• ISSNs: 0364-5134

Abstract

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