title: Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy.
abstract: We investigated the genetic background of early-onset epileptic encephalopathy (EE) using targeted next generation sequencing analysis. Thirty sporadic or familial cases associated with early-onset EE were included. An early-onset EE gene panel including sixteen genes (ARX, CDKL5, CNTNAP2, FOLR1, FOXG1, LAMC3, MBD5, MECP2, NTNG1, PCDH19, PNKP, SCN1A, SCN1B, SCN2A, STXBP1, KCNQ2) was constituted. Nine definite and three potential causal mutations in 30 cases (40 %) were identified. All mutations presented heterozygously except one. Five mutations had been previously detected (SCN1A c.842C > T (p.P281L), SCN1A c.4907G > C (p.A1636P), PCDH19 c.1091dupC (p.Y366LfsX10), CNTNAP2 c.416A > G (p.N139S), MBD5 c.3595G > A(p.Y1199R) while other seven were novel (SCN1A c.4907G > C (p.A1636P), SCN2A c.4633A > G (p.M1545 V), CDKL5 c.197_198delCT (p.L67QfsX23), FOXG1 c.*6C > T, KCNQ2 c.560c > A (p.S187Y), KCNQ2 c.835G > A (p.G279S), STXBP1 c.1105G > T (p.E369X)). Eight of 12 mutations were de novo. While the overall mutation detection rate was found 40 %, this ratio was 55.5 % (10 out of 18) and 16.6 % (2 out of 12) in patients born to nonconsanguineous parents and consanguineous parents, respectively. In conclusion, a selected gene panel approach including mainly de novo and channel-encoding genes will result in the detection of variants in isolated patients and support the channelopathy theory underlying epilepsy, while consanguineous families will remain less diagnosed. Targeted next generation sequencing approach is an efficient diagnostic tool in the detection of the genetic basis of early-onset EE.
authors.affiliation: Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Izmir, Turkey.
authors.forename: Sarenur
authors.initials: S
authors.lastname: Gokben
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Onay
authors.affiliation: Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Izmir, Turkey. sanem.yilmaz@ege.edu.tr.
authors.forename: Sanem
authors.initials: S
authors.lastname: Yilmaz
authors.affiliation: Division of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Tahir
authors.initials: T
authors.lastname: Atik
authors.affiliation: Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Izmir, Turkey.
authors.forename: Gul
authors.initials: G
authors.lastname: Serdaroglu
authors.affiliation: Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Izmir, Turkey.
authors.forename: Hande
authors.initials: H
authors.lastname: Tekin
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.|Division of Pediatric Genetics, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
authors.forename: Ferda
authors.initials: F
authors.lastname: Ozkinay
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D013036:Spasms, Infantile / Q000235:genetics*
keywords: Early-onset; Epileptic encephalopathy; Genetic background; Targeted next generation sequencing