Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype
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e282.full.pdf
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Published version
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810.27 KB
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Author(s)
Guan, Zhou
Littleton, J. Troy
Date Issued
December 2018
Journal
Neurology: Genetics
Publisher
Ovid Technologies (Wolters Kluwer Health)
Citation
Montes-Chinea, Nataly I. et al. “Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype.” Neurology: Genetics 4 (2018): e282 © 2018 The Author(s)
Version
Final published version
Abstract
Objective To report a new SYT2 missense mutation causing distal hereditary motor neuropathy and presynaptic neuromuscular junction (NMJ) transmission dysfunction. Methods We report a multigenerational family with a new missense mutation, c. 1112T>A (p. Ile371Lys), in the C2B domain of SYT2, describe the clinical and electrophysiologic phenotype associated with this variant, and validate its pathogenicity in a Drosophila model. Results Both proband and her mother present a similar clinical phenotype characterized by a slowly progressive, predominantly motor neuropathy and clear evidence of presynaptic NMJ dysfunction on nerve conduction studies. Validation of this new variant was accomplished by characterization of the mutation homologous to the human c. 1112T>A variant in Drosophila, confirming its dominant-negative effect on neurotransmitter release. Conclusions This report provides further confirmation of the role of SYT2 in human disease and corroborates the resultant unique clinical phenotype consistent with heriditary distal motor neuropathy. SYT2-related motor neuropathy is a rare disease but should be suspected in patients presenting with a combination of presynaptic NMJ dysfunction (resembling Lambert-Eaton myasthenic syndrome) and a predominantly motor neuropathy, especially in the context of a positive family history.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1212/NXG.0000000000000282
