期刊
ANNALS OF NEUROLOGY
卷 81, 期 4, 页码 597-603出版社
WILEY
DOI: 10.1002/ana.24905
关键词
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资金
- Wellcome Trust [WT093205MA, WT104033AIA]
- Medical Research Council
- European Community [2012-305121]
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- National Institutes of Health (NIH) [NS-055028]
- Medical Research Council [G1001253, G0802760, G108/638, MR/J004758/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10082] Funding Source: researchfish
- MRC [G1001253, MR/J004758/1, G0802760, G108/638] Funding Source: UKRI
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.
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