Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

SYNAPS Study Group; Yun Liu

doi:10.1002/ana.24905

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

SYNAPS Study Group, Yun Liu

Research output: Contribution to journal › Article › peer-review

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Abstract

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 VAMP1^lew/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.

Original language	English (US)
Pages (from-to)	597-603
Number of pages	7
Journal	Annals of Neurology
Volume	81
Issue number	4
DOIs	https://doi.org/10.1002/ana.24905
State	Published - Apr 2017

ASJC Scopus subject areas

Neurology
Clinical Neurology

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title = "Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome",

abstract = "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.",

author = "{SYNAPS Study Group} and Vincenzo Salpietro and Weichun Lin and Vedove, {Andrea Delle} and Yun Liu and Yun Liu and Stephanie Efthymiou and Andreea Manole and Sarah Wiethoff and Qiaohong Ye and Anand Saggar and Kenneth McElreavey and Krishnakumar, {Shyam S.} and Matthew Pitt and Bello, {Oscar D.} and Rothman, {James E.} and Lina Basel-Vanagaite and Hubshman, {Monika Weisz} and Sharon Aharoni and Manzur, {Adnan Y.} and Brunhilde Wirth and Henry Houlden",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors. Annals of Neurology Published by Wiley Periodicals, Inc.",

year = "2017",

month = apr,

doi = "10.1002/ana.24905",

language = "English (US)",

volume = "81",

pages = "597--603",

journal = "Annals of Neurology",

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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 - 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

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.

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Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

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