METHODS: Targeted panel sequencing was performed on 96 patients with a strong clinical suspicion of genetic focal epilepsy. Patients had previously gone through a comprehensive diagnostic epilepsy evaluation in The Neurology Clinic, University Clinical Center of Serbia. Variants of interest (VOI) were classified using the American College of Medical Genetics and the Association for Molecular Pathology criteria.
RESULTS: Six VOI in eight (8/96, 8.3%) patients were found in our cohort. Four likely pathogenic VOI were determined in six (6/96, 6.2%) patients, two DEPDC5 variants in two patients, one SCN1A variant in two patients and one PCDH19 variant in two patients. One variant of unknown significance (VUS) was found in GRIN2A in one (1/96, 1.0%) patient. Only one VOI in GRIN2A was classified as likely benign. No VOI were detected in LGI1.
CONCLUSIONS: Sequencing of only five known epilepsy genes yielded a diagnostic result in 6.2% of our cohort and revealed multiple novel variants. Further research is necessary for a better understanding of the genetic basis in common epilepsy syndromes in patients with normal intellectual function or mild intellectual disability.
方法:对96例临床怀疑为遗传性局灶性癫痫的患者进行了靶向组测序。患者以前在神经内科诊所进行过全面的癫痫诊断评估,塞尔维亚大学临床中心。使用美国医学遗传学学会和分子病理学协会标准对感兴趣的变体(VOI)进行分类。
结果:在我们的队列中发现了8例(8/96,8.3%)患者中的6例VOI。在6例(6/96,6.2%)患者中确定了4种可能的致病性VOI,两名患者的两种DEPDC5变体,两名患者中有一个SCN1A变体,两名患者中有一个PCDH19变体。在一名(1/96,1.0%)患者的GRIN2A中发现了一种未知意义的变体(VUS)。GRIN2A中只有一个VOI被归类为可能的良性。在LGI1中未检测到VOI。
结论:仅对5个已知癫痫基因的测序在我们队列中的6.2%中产生了诊断结果,并揭示了多个新的变异。需要进一步的研究才能更好地了解智力正常或轻度智力残疾患者常见癫痫综合征的遗传基础。