No association between SCN9A and monogenic human epilepsy disorders.
No association between SCN9A and monogenic human epilepsy disorders.
复制标题
DOI：
10.1371/journal.pgen.1009161
复制
发表时间：
2020-11
期刊：
影响因子：
4.5
通讯作者：
Baple EL
中科院分区：
文献类型：
--
作者：
Fasham J;Leslie JS;Harrison JW;Deline J;Williams KB;Kuhl A;Scott Schwoerer J;Cross HE;Crosby AH;Baple EL
许多研究表明，癫痫基因组检测在确认疾病的具体病因、进行适当的治疗干预和提供准确的家庭咨询方面具有临床效用和重要性。以前，SCN9A基因变异，特别是c.1921A>T p.（Asn641Tyr）替换，已被确定为可能的常染色体显性原因，导致发热性癫痫发作/发热性癫痫发作加和其他单基因癫痫表型与SCN1A相关的表型无法区分，导致SCN9A被纳入癫痫基因检测小组。在这里，我们提出了遗传研究的偶然发现，在没有这种癫痫表型的阿米什社区中，SCN9A c.1921A>T . p.（Asn641Tyr）变异频率很高。与英国生物银行的发现一起，这些数据驳斥了SCN9A与癫痫的关联，这具有重要的临床诊断意义。癫痫被定义为一种癫痫发作的倾向，全世界约有1:100人受其影响。一些遗传类型的癫痫可以通过一项测试来诊断，该测试检查了先前被证明在受基因改变影响时导致癫痫的基因。确定患者癫痫的遗传原因可以帮助确定哪些治疗可能有用，提供预后信息，并告知准确的家庭咨询。被纳入癫痫诊断基因检测小组的基因是通过审查已发表的科学研究来决定的。以前的出版物描述了SCN9A基因与癫痫形式之间的关联，导致SCN9A基因被纳入诊断测试小组。在本文中，我们介绍了我们的遗传发现的结果，并在阿米什社区和英国生物银行对SCN9A基因改变的后续研究，以及对先前研究SCN9A在癫痫中的作用的新评估。总之，我们的发现有力地驳斥了SCN9A与癫痫之间的关联。这项工作具有重要的临床意义，应该导致专家小组重新评估SCN9A并将其从基因检测小组中移除，防止未来可能具有破坏性甚至有时致命后果的基因误诊。
Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family counselling. Previously, SCN9A gene variants, in particular a c.1921A>T p.(Asn641Tyr) substitution, have been identified as a likely autosomal dominant cause of febrile seizures/febrile seizures plus and other monogenic seizure phenotypes indistinguishable from those associated with SCN1A, leading to inclusion of SCN9A on epilepsy gene testing panels. Here we present serendipitous findings of genetic studies that identify the SCN9A c.1921A>T p.(Asn641Tyr) variant at high frequency in the Amish community in the absence of such seizure phenotypes. Together with findings in UK Biobank these data refute an association of SCN9A with epilepsy, which has important clinical diagnostic implications. Epilepsy is defined as a tendency to have seizures, affecting around 1:100 people worldwide. Some genetic types of epilepsy can be diagnosed using a test that examines genes that have previously been shown to cause epilepsy when affected by genetic alterations. Identifying the genetic cause of a patient’s epilepsy can help determine which treatments are likely to be helpful, provide prognostic information and inform accurate family counselling. The genes that are included in diagnostic epilepsy gene testing panels are decided by reviewing published scientific studies. Previous publications have described an association between the SCN9A gene and forms of epilepsy, leading to inclusion of the SCN9A gene in diagnostic testing panels. In this paper we present the results of our genetic findings and follow-up studies of SCN9A gene alterations in the Amish community and UK Biobank, alongside a fresh appraisal of previous studies investigating the role of SCN9A in epilepsy. Together our findings strongly refute an association between SCN9A and epilepsy. This work has important clinical implications and should lead to the re-evaluation of SCN9A by expert groups and its removal from genetic testing panels, preventing future genetic misdiagnosis which may have devastating and sometimes lethal consequences.
登录
查看更多内容
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
11.2
作者：
Faber, Catharina G.;Hoeijmakers, Janneke G. J.;Merkies, Ingemar S. J.
通讯作者：
Merkies, Ingemar S. J.
影响因子：
--
作者：
Michiels, JJ;te Morsche, RHM;Drenth, JPH
通讯作者：
Drenth, JPH
SCN9A 基因 Q1OR 突变与全身性癫痫伴热性惊厥相关
影响因子：
3
作者：
Cen, Zhidong;Lou, Yuting;Feng, Jianhua
通讯作者：
Feng, Jianhua
影响因子：
2.5
作者：
Balestrini S;Sisodiya SM
通讯作者：
Sisodiya SM