PT  - JOURNAL ARTICLE
AU  - Nataly I. Montes-Chinea
AU  - Zhuo Guan
AU  - Marcella Coutts
AU  - Cecilia Vidal
AU  - Steve Courel
AU  - Adriana P. Rebelo
AU  - Lisa Abreu
AU  - Stephan Zuchner
AU  - J. Troy Littleton
AU  - Mario A. Saporta
TI  - Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype
AID  - 10.1212/NXG.0000000000000282
DP  - 2018 Dec 01
TA  - Neurology Genetics
PG  - e282
VI  - 4
IP  - 6
4099  - http://ng.neurology.org/content/4/6/e282.short
4100  - http://ng.neurology.org/content/4/6/e282.full
SO  - Neurol Genet2018 Dec 01; 4
AB  - 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.ADM=abductor digiti minimi; AH=abductor hallucis; ANOVA=analysis of variance; APB=abductor pollicis brevis; CMT=Charcot-Marie-Tooth; CMTNS=Charcot-Marie-Tooth Neuropathy Score; dHMN=Hereditary distal motor neuropathy; eEJC=excitatory evoked junctional current; NMJ=neuromuscular junction; RNS=repetitive nerve stimulation; WT=wildtype