VAMP1基因的纯合突变会导致一种突触前先天性肌无力综合征。
Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
作者信息
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
机构信息
Department of Molecular Neuroscience, Institute of Neurology, University College London Institute of Neurology, London, United Kingdom.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX.
出版信息
Ann Neurol. 2017 Apr;81(4):597-603. doi: 10.1002/ana.24905. Epub 2017 Mar 29.
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 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.
我们报告了2个患有未确诊的隐性突触前先天性肌无力综合征（CMS）的家族。全外显子组或基因组测序在VAMP1中鉴定出分离的纯合变异：一个科威特家族中的c.51_64delAGGTGGGGGTCCCC和一个以色列家族中的c.146G>C。VAMP1对于突触前神经肌肉接头（NMJ）处的囊泡融合至关重要。电诊断检查显示复合肌肉动作电位严重降低以及突触前功能障碍。我们评估了无义突变对mRNA水平的影响，并在VAMP1小鼠中评估了NMJ传递，观察到与患者相似的突触前功能障碍的神经生理学特征。综上所述，我们的研究结果突出了VAMP1纯合突变是突触前CMS的一个病因。《神经病学纪事》2017年；81:597 - 603。
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