自然受孕两胎 ，都早产且都是剖腹产 第一胎 胎盘大 ，第二胎 脐带细 ， 两胎都在出生三月开始癫痫发作 ， 第二胎，染色体检查正常，基因检查宝宝为“GABRA6 基因发现c.136c>t的杂合优艾设计网_PS论坛核苷酸变异，该变异导致第46号氨基酸由ARG变为TRP，为错义变异，可能对蛋白质功能造成影响。受检者其父该点位未见异常，其母该位点为杂合子。” 想问下这种情况是不是宝宝就是这个基因引起癫痫的 母亲本身没有病症 也没有家族遗传史
医生说不是这个基因引起的，建议做全外显子组测序，请教各位改怎么办？这是什么情况？
ty_114469168 2021-10-27 20:14 优艾设计网_Photoshop问答
癫痫有20%－30%是单基因引起的，华大有这个panel可以筛一下。
ty_114469168 优艾设计网_PS问答 2021-10-27 20:23
从这个结果来看，孩子和母亲的基因型是一样的，但母亲没有发病，不符合经典的遗传学规律，应该不是致病基因。
董加贝 2021-10-27 20:37
解读报告在于对疾病是否致病的每个解释要有依据：
首先，分析一下这份报告：
①GABRA6这个基因在OMIM上的解释为：Gamma-aminobutyric acid (GABA) receptors are a family of proteins involved in the GABAergic neurotransmission of the mammalian central nervous system. GABRA6 is a member of the GABA-A receptor gene family of heteromeric pentameric ligand-gated ion channels through which GABA, the major inhibitory neurotransmitter in the mammalian brain, acts.(summary by Whiting et al., 1999).也就是说这个基因是γ-氨基丁酸受体家族的成员之一，参与哺乳动物中枢神经系统的神经传递。
②c.136C>T为错义突变，判断是否致病需要按照一定的解读规则。
③p.Arg46Trp，蛋白的功能是否发生改变，这个是要体外、体内试验或功能软件预测；或者有文献依据。
④PubMed：21930603的文献中是这样描述的：Childhood absence epilepsy (CAE) is a genetic form of epilepsy that typically develops at 4 –8 years of age with brief losses of consciousness and frequent staring spells. Genetic defects or mutations associated with this disorder have been found in specialized
membrane proteins called GABAA receptor channels. GABAA receptors are ligand - gated chloride
channels, and the majority are thought to be composed of α , β and γ or α , β and δ subunit
proteins that mediate both rapid, phasic inhibitory ynaptic t r a nsmission and s teady-state, tonic
perisynaptic inhibition in the nervous system. Here we showed that a novel GABA A receptor α 6 subunit mutation linked with CAE, R46W, impaired gating and assembly of both αβγ and αβδ GABAA receptors. These findings suggested that the CAE-associated α 6(R46W ) subunit mutation could cause neuronal disinhibition and thus increase susceptibility to generalized seizures through a reduction of αβγ and αβδ receptor function and expression.报告中引用的这篇文献是讲GABRA6基因的c.136C>T突变与Childhood absence epilepsy疾病的关系，这个突变导致神经元去抑制，通过降低αβγ和αβδ 受体的功能和表达来增加癫痫的敏感性。So，这个点的致病性是肯定的。
⑤报告中提到的疾病：Idiopathic generalized epilepsy (IGE) 在wiki上的概念是：is a group of epileptic disorders that are believed to have a strong underlying genetic basis. Patients with an IGE subtype are typically otherwise normal and have no structural brain abnormalities. Patients also often have a family history of epilepsy and seem to have a genetically predisposed risk of seizures. IGE tends to manifest itself between early childhood a优艾设计网_设计百科nd adolescence although it can be eventually diagnosed later. The genetic cause of some IGE types is known, though inheritance does not always follow a simple monogenic mechanism.这是一组疾病，而且包含了复杂疾病，发病的类型也大不相同，从婴儿发病到青春期发病都有，而且复杂疾病还要考虑其他基因等综合因素，而且遗传方式我目前还没有查到。
终上所述，GABRA6基因的c.136C>T突变在患儿的发病过程中可能起到作用。但是真正发病的原因还要对2个患儿同时进行检测和分析。
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