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KIF5A mutations cause an infantile onset phenotype including severe myoclonus with evidence of mitochondrial dysfunction
Author(s) -
Duis Jessica,
Dean Shan,
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.
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24744
Subject(s) - missense mutation , frameshift mutation , myoclonus , exome sequencing , hypotonia , phenotype , medicine , genetics , spastic , pediatrics , neuroscience , bioinformatics , biology , physical medicine and rehabilitation , cerebral palsy , gene
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