TY - JOUR
T1 - Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome
AU - SYNAPS Study Group
AU - Salpietro, Vincenzo
AU - Lin, Weichun
AU - Vedove, Andrea Delle
AU - Storbeck, Markus
AU - Liu, Yun
AU - Efthymiou, Stephanie
AU - Manole, Andreea
AU - Wiethoff, Sarah
AU - Ye, Qiaohong
AU - Saggar, Anand
AU - McElreavey, Kenneth
AU - Krishnakumar, Shyam S.
AU - Pitt, Matthew
AU - Bello, Oscar D.
AU - Rothman, James E.
AU - Basel-Vanagaite, Lina
AU - Hubshman, Monika Weisz
AU - Aharoni, Sharon
AU - Manzur, Adnan Y.
AU - Wirth, Brunhilde
AU - Houlden, Henry
N1 - Publisher Copyright:
© 2017 The Authors. Annals of Neurology Published by Wiley Periodicals, Inc.
PY - 2017/4
Y1 - 2017/4
N2 - We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1lew/lew mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597–603.
AB - We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1lew/lew mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597–603.
UR - https://www.scopus.com/pages/publications/85018473314
U2 - 10.1002/ana.24905
DO - 10.1002/ana.24905
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C2 - 28253535
AN - SCOPUS:85018473314
SN - 0364-5134
VL - 81
SP - 597
EP - 603
JO - Annals of Neurology
JF - Annals of Neurology
IS - 4
ER -