The ClinGen Epilepsy Gene Curation Expert Panel-Bridging the divide between clinical domain knowledge and formal gene curation criteria
The ClinGen Epilepsy Gene Curation Expert Panel-Bridging the divide between clinical domain knowledge and formal gene curation criteria
复制标题
DOI：
10.1002/humu.23632
复制
发表时间：
2018-11-01
期刊：
影响因子：
3.9
通讯作者：
Mefford, Heather C.
中科院分区：
文献类型：
--
作者：
Helbig, Ingo;Riggs, Erin Rooney;Mefford, Heather C.
癫痫遗传学领域正在迅速发展，癫痫正在成为诊断性基因检测的常见指征。在更大的ClinGen框架内，ClinGen癫痫基因治疗专家小组的任务是连接两个日益独立的领域：传统的临床癫痫学领域，有自己建立的语言和分类标准，以及快速发展的诊断基因检测领域，坚持基因和变异治疗的正式标准。我们确定了癫痫基因治疗工作的关键组成部分，包括：（a）现有疾病和表型本体内的精确表型定义;（B）考虑癫痫何时应作为一个独特的疾病实体进行治疗;（c）基因选择策略;（d）评估癫痫发作疾病功能模型的新兴规则。鉴于新生变异在许多癫痫中起着重要作用，因此在治疗过程的早期通常会获得足够的遗传证据。因此，基因策展的重点经常转向迭代预策展过程，以更好地捕获表型关联。我们证明，在神经发育障碍的范围内，癫痫相关基因的基因治疗是可行的，并建议癫痫特定的公约，奠定了基础的所有主要癫痫相关基因的治疗过程。
The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes.