Author:
Montes-Chinea Nataly I.,Guan Zhuo,Coutts Marcella,Vidal Cecilia,Courel Steve,Rebelo Adriana P.,Abreu Lisa,Zuchner Stephan,Littleton J. Troy,Saporta Mario A.
Abstract
ObjectiveTo report a new SYT2 missense mutation causing distal hereditary motor neuropathy and presynaptic neuromuscular junction (NMJ) transmission dysfunction.MethodsWe 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.ResultsBoth 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.ConclusionsThis 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics(clinical),Clinical Neurology
Cited by
22 articles.
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