Debate: Does genetic information in humans help us treat patients? PRO--genetic information in humans helps us treat patients. CON--genetic information does not help at all.-猫眼课题宝

辩论：人类的遗传信息是否有助于我们治疗患者？

DOI：

10.1111/j.1528-1167.2008.01922.x

发表时间：

2008

期刊：

Epilepsia

影响因子：

5.6

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Delgado-Escueta,AntonioV;Bourgeois,BlaiseFD

PRO—总结在过去的十年中，基因分型已开始帮助神经科医生治疗患有三种类型癫痫引起突变的患者，即（1）SCN1A，一种在 Dravet 婴儿散发性严重肌阵挛性癫痫（SMEI 和 SMEB）中突变的钠通道基因； (2) Lafora 进行性肌阵挛癫痫 (PME) 中的 Laforin（双特异性蛋白磷酸酶）和 malin（泛素 E3 连接酶）； (3) Unverricht-Lundborg 型 PME 中的胱抑素 B。 Laforin、malin 和胱抑素 B 是导致 PME 的非离子通道基因突变。基因分型可确保准确的诊断，帮助治疗和遗传咨询，为患者和家庭提供心理和社会帮助，并引导家庭前往致力于寻找特定癫痫疾病治疗方法的组织。对于 SCN1A 和胱抑素 B 突变，应避免使用钠通道阻滞剂（苯妥英、卡马西平、奥卡西平、拉莫三嗪）治疗。由于通过 SCN1 突变基因分型进行早期正确诊断、避免使用钠通道阻滞剂以及积极治疗长期惊厥状态，Dravet 综合征有望不像过去所有报告中观察到的那么严重。基因分型还可以识别 Lafora PME 中的无义突变。无义突变可以通过过早终止密码子通读药物（例如庆大霉素）来纠正。社区从业者与 PME 中的癫痫专家可以共同努力，获取庆大霉素（Barton-Davis 等，1999）用于 Lafora PME 的“同情使用”，Lafora PME 是一种普遍的溶酶体多器官贮积症，总是致命的。在Unverricht-Lundborg PME中，具有基因型胱抑素B突变的新队列导致长期使用抗氧化剂N-乙酰半胱氨酸和丙戊酸钠氯巴扎或氯硝西泮联合抗肌阵挛药物托吡酯、唑尼沙胺、吡拉西坦、左乙拉西坦或布瓦西坦。这些队列有轻微的共济失调且没有痴呆，质疑该综合征是否真正进展。总之，基因分型不仅是诊断 Dravet 综合征和进行性肌阵挛癫痫的先决条件，而且还有助于我们选择正确的抗癫痫药物来治疗 Dravet 综合征和 Unverricht-Lundborg PME 的癫痫发作。基因分型也预示着更光明的未来，帮助我们重新评估 Dravet 综合征和 Unverricht-Lundborg PME 的真实病程、严重程度和进展性质，并帮助我们为 Dravet 综合征和 Lafora 病制定未来的治疗方法。如果没有引起突变的癫痫基因分型诊断，我们就会陷入不精确的诊断和癫痫发作的对症治疗。CON—总结癫痫的基因分型可能有助于更好地了解癫痫的遗传学，确定癫痫患者的病因，提供遗传咨询，并确认临床诊断。然而，批判性分析表明，基因分型无助于改善患者的治疗。为了改善治疗，基因分型必须（1）提高我们为特定癫痫或癫痫综合征选择药物的能力；（2）提高我们预测某些药物不良反应个体风险的能力； (3) 提高我们避免不必要的治疗或可能加重癫痫发作的治疗的能力。许多例子说明了遗传信息对治疗结果的影响的缺乏：自从SCN1A检测可用以来，我们并没有更成功地治疗Dravet综合征；自从可以进行拉福林和马林检测以来，我们并没有更成功地治疗拉福拉病；我们不需要知道 Unverricht-Lundborg 的遗传本质……

PRO—SummaryIn the past decade, genotyping has started to help the neurologic practitioner treat patients with three types of epilepsy causing mutations, namely (1)SCN1A, a sodium channel gene mutated in Dravet’s sporadic severe myoclonic epilepsy of infancy (SMEI and SMEB); (2) laforin (dual specificity protein phosphatase) and malin (ubiquitin E3 ligase) in Lafora progressive myoclonic epilepsy (PME); and (3) cystatin B in Unverricht‐Lundborg type of PME. Laforin, malin, and cystatin B are non–ion channel gene mutations that cause PME. Genotyping ensures accurate diagnosis, helps treatment and genetic counseling, psychological and social help for patients and families, and directs families to organizations devoted to finding cures for specific epilepsy diseases. InSCN1Aand cystatin B mutations, treatment with sodium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine) should be avoided. Because of early and correct diagnosis by genotyping ofSCN1Amutations, the avoidance of sodium channel blockers, and aggressive treatment of prolonged convulsive status, there is hope that Dravet’s syndrome may not be as severe as observed in all past reports. Genotyping also identifies nonsense mutations in Lafora PME. Nonsense mutations can be corrected by premature stop codon readthrough drugs such as gentamicin. The community practitioner together with epilepsy specialists in PME can work together and acquire gentamicin (Barton‐Davis et al., 1999) for “compassionate use” in Lafora PME, a generalized lysosome multiorgan storage disorder that is invariably fatal. In Unverricht‐Lundborg PME, new cohorts with genotyped cystatin B mutations have led to the chronic use of antioxidantN‐acetylcysteine and combination valproate clobazam or clonazepam plus antimyoclonic drugs topiramate, zonisamide, piracetam, levetiracetam, or brivaracetam. These cohorts have minimal ataxia and no dementia, questioning whether the syndrome is truly progressive. In conclusion, not only is genotyping a prerequisite in the diagnosis of Dravet’s syndrome and the progressive myoclonus epilepsies, but it also helps us choose the correct antiepileptic drugs to treat seizures in Dravet’s syndrome and Unverricht‐Lundborg PME. Genotyping also portends a brighter future, helping us to reassess the true course, severity, and progressive nature of Dravet’s syndrome and Unverricht‐Lundborg PME and helping us craft a future curative treatment for Dravet’s syndrome and Lafora disease. Without the genotyping diagnosis of epilepsy causing mutations we are stuck with imprecise diagnosis and symptomatic treatment of seizures.CON—SummaryGenotyping of epilepsy may help to better understand the genetics of epilepsy, to establish an etiology in a patient with epilepsy, to provide genetic counseling, and to confirm a clinical diagnosis. However, critical analysis reveals that genotyping does not contribute to an improved treatment for the patients. In order to improve treatment, genotyping would have to (1) improve our ability to select the drug of choice for a given epilepsy or epileptic syndrome; (2) improve our ability to predict the individual risk of adverse reactions to certain drugs; (3) improve our ability to avoid unnecessary treatments or treatments that could aggravate seizures.Many example illustrate the lack of impact of genetic information on the treatment outcome: we do not treat Dravet syndrome more successfully since SCN1A testing became available; we do not treat Lafora disease more successfully since testing for laforin and malin became available; we do not need to know the genetic nature of Unverricht‐Lundborg …

Debate: Does genetic information in humans help us treat patients? PRO--genetic information in humans helps us treat patients. CON--genetic information does not help at all.

辩论：人类的遗传信息是否有助于我们治疗患者？

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