Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes

作者：Parrini Elena; Marini Carla; Mei Davide; Galuppi Anna; Cellini Elena; Pucatti Daniela; Chiti Laura; Rutigliano Domenico; Bianchini Claudia; Virdo Simona; De Vita Dalila; Bigoni Stefania; Barba Carmen; Mari Francesco; Montomoli Martino; Pisano Tiziana; Rosati Anna; Guerrini Renzo

来源：Human Mutation, 2017, 38(2): 216-225.

DOI：10.1002/humu.23149

• epilepsy
• next-generation sequencing
• gene panel
• mutation

Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of mutation positive patients, epilepsy onset occurred before the age of 6 months. The 95-genes panel allowed a genetic diagnosis in 22 (6.3%) patients that would have otherwise been missed using the 30-gene panel. About 50% of mutations were identified in genes coding for sodium and potassium channel components. SCN2A was the most frequently mutated gene followed by SCN1A, KCNQ2, STXBP1, SCN8A, CDKL5, and MECP2. Twenty-nine mutations were identified in 23 additional genes, most of them recently associated with epilepsy. Our data show that panels targeting about 100 genes represent the best cost-effective diagnostic option in pediatric drug-resistant epilepsies. They enable molecular diagnosis of atypical phenotypes, allowing to broaden phenotype-genotype correlations. Molecular diagnosis might influence patients' management and translate into better and specific treatment recommendations in some conditions.

• 出版日期2017-2