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

Funding

FundersFunder number
FP7/20072012-305121
National Institute for Health Research University College London Hospitals Biomedical Research Centre
National Institutes of Health
National Institute of Neurological Disorders and StrokeR01NS055028
Wellcome TrustWT104033AIA, WT093205MA
Medical Research Council
Seventh Framework Programme

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