Homozygous Mutations in VAMP1 Cause a Presynaptic Congenital Myasthenic Syndrome

作者：Salpietro Vincenzo; Lin Weichun; Delle Vedove Andrea; Storbeck Markus; Liu Yun; Efthymiou Stephanie; Manole Andreea; Wiethoff Sarah; Ye Qiaohong; Saggar Anand; McElreavey Kenneth; Krishnakumar Shyam S; Pitt Matthew; Bello Oscar D; Rothman James E; Basel Vanagaite Lina; Hubshman Monika Weisz; Aharoni Sharon; Manzur Adnan Y; Wirth Brunhilde^*; Houlden Henry^*

来源：Annals of Neurology, 2017, 81(4): 597-603.

DOI：10.1002/ana.24905

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.

• 出版日期2017-4