Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability.
Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability.
复制标题
DOI：
10.4161/rdis.26314
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Chung WK
中科院分区：
文献类型：
--
作者：
Rohena L;Neidich J;Truitt Cho M;Gonzalez KD;Tang S;Devinsky O;Chung WK
全外显子组测序使用亲子三重设计来鉴定从头突变提供了一种有效的方法来鉴定具有低生殖适应性的罕见疾病的新基因，这些罕见疾病难以通过更经典的遗传学方法进行研究。我们报告一位15岁的女性，患有严重的静止性脑病、智力障碍及全身性癫痫。经过广泛的代谢和遗传测试，全外显子组测序鉴定了突触体相关蛋白-25（SNAP 25）的一种新的从头变异，c.142G > T p.Phe48Val改变。所有预测算法都预测这种变体具有破坏性。SNAP 25是可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白复合物的一部分，其参与神经递质的胞吐释放。在动物模型中，Snap 25的遗传改变可导致焦虑相关行为、共济失调和癫痫发作。我们认为人类SNAP 25突变是智力残疾和癫痫的一种新的遗传原因。
Whole exome sequencing using a parent-child trio design to identify de novo mutations provides an efficient method to identify novel genes for rare diseases with low reproductive fitness that are difficult to study by more classical genetic methods of linkage analysis. We describe a 15 y old female with severe static encephalopathy, intellectual disability, and generalized epilepsy. After extensive metabolic and genetic testing, whole exome sequencing identified a novel de novo variant in Synaptosomal-associated protein-25 (SNAP25), c.142G > T p.Phe48Val alteration. This variant is predicted to be damaging by all prediction algorithms. SNAP25 is part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein complex which is involved in exocytotic release of neurotransmitters. Genetic alterations in Snap25 in animal models can cause anxiety-related behavior, ataxia and seizures. We suggest that SNAP25 mutations in humans are a novel genetic cause of intellectual disability and epilepsy.