KIF5Amutations cause an infantile onset phenotype including severe myoclonus with evidence of mitochondrial dysfunction
| Autor: | Lisa R. Sun, Marta Biderman Waberski, James D. Dollar, Shannon L. Dean, Ada Hamosh, Amy Harper, Carl E. Stafstrom, Jessica Duis, Carolyn D. Applegate, Rui Xiao, Thomas O. Crawford, Weimin He |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mutation Pathology medicine.medical_specialty Muscle Hypotonia Biology medicine.disease_cause Hypotonia Frameshift mutation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Neurology medicine Spastic Missense mutation Kinesin Neurology (clinical) medicine.symptom Myoclonus 030217 neurology & neurosurgery |
| Zdroj: | Annals of Neurology. 80:633-637 |
| ISSN: | 0364-5134 |
| DOI: | 10.1002/ana.24744 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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