Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

SYNAPS Study Group, Yun Liu

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)597-603
Number of pages7
JournalAnnals of Neurology
Volume81
Issue number4
DOIs
StatePublished - Apr 2017

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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