Ortega-Moreno Laura, Giráldez Beatriz G, Soto-Insuga Victor, Losada-Del Pozo Rebeca, Rodrigo-Moreno María, Alarcón-Morcillo Cristina, Sánchez-Martín Gema, Díaz-Gómez Esther, Guerrero-López Rosa, Serratosa José M
Neurology Lab and Epilepsy Unit, Department of Neurology, IIS- Fundación Jiménez Díaz, UAM, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
PLoS One. 2017 Nov 30;12(11):e0188978. doi: 10.1371/journal.pone.0188978. eCollection 2017.
Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify disease-causing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsy-associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13, CHD2, SYNGAP1, and GRIN1). Twelve of 18 variants arose de novo and 6 were novel. The highest yield was found in patients with onset in the first years of life, especially in patients classified as having early-onset epileptic encephalopathy. Knowledge of the underlying genetic cause provides essential information on prognosis and could be used to avoid unnecessary studies, which may result in a greater diagnostic cost-effectiveness.
小儿癫痫是一组具有广泛表型谱的疾病，与巨大的遗传异质性相关，因此连续单基因检测作为诊断策略的基础并不实用。下一代测序技术的出现提高了癫痫诊断的成功率，使用基因panel进行靶向重测序是最具成本效益的选择。我们报告了一组87例癫痫伴发育迟缓患者使用靶向下一代测序（定制设计的Haloplex panel）的结果。使用该基因panel，我们在87例分析患者中的17例（19.5%）中鉴定出致病变异，均在已知的癫痫相关基因（KCNQ2、CDKL5、STXBP1、SCN1A、PCDH19、POLG、SLC2A1、ARX、ALG13、CHD2、SYNGAP1和GRIN1）中发现。18个变异中有12个是新发的，6个是新发现的。在生命最初几年发病的患者中检出率最高，尤其是被归类为早发性癫痫性脑病的患者。了解潜在的遗传病因可提供有关预后的重要信息，并可用于避免可能导致更高诊断成本效益的不必要检查。
