This study reports 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 required for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. The effect of the nonsense mutation on mRNA levels was assessed and the NMJ transmission in VAMP1lew/lew mice evaluated, observing neurophysiological features of presynaptic impairment, similar to the patients.
