Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28253535.
- Also identified by DOI 10.1002/ana.24905 and PMC identifier 5413866.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>lew/lew</sup> 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.
Medical subject headings
- Myasthenic Syndromes, Congenital
- Neuromuscular Junction
- Vesicle-Associated Membrane Protein 1