title: Unexplained Early Infantile Epileptic Encephalopathy in Han Chinese Children: Next-Generation Sequencing and Phenotype Enriching.
abstract: Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures and progressive disturbance of cerebral function. This study was to investigate a cohort of Chinese children with unexplained EIEE, infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We used targeted next-generation sequencing to identify potential pathogenic variants of 308 genes in 68 Han Chinese patients with unexplained EIEE. A filter process was performed to prioritize rare variants of potential functional significance. In all cases where parental testing was accessible, Sanger sequencing confirmed the variants and determined the parental origin. In 15% of patients (n = 10/68), we identified nine de novo pathogenic variants, and one assumed de novo pathogenic variant in the following genes: CDKL5 (n = 2), STXBP1 (n = 2), SCN1A (n = 3), KCNQ2 (n = 2), SCN8A (n = 1), four of the variants are novel variants. In 4% patients (n = 3/68), we identified three likely pathogenic variants; two assumed de novo and one X-linked in the following genes: SCN1A (n = 2) and ARX (n = 1), two of these variants are novel. Variants were assumed de novo when parental testing was not available. Our findings were first reported in Han Chinese patients with unexplained EIEE, enriching the EIEE mutation spectrum bank.
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Arafat
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jing
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Pu
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Gai
authors.initials: G
authors.lastname: Nan
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Fang
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Xiang Ya First Hospital of Central South University, China, 87 Xiang ya road, Changsha, Hunan, 410008, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Fei
mesh_terms: D000367:Age Factors; D044466:Asian People; D004569:Electroencephalography; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D011159:Population Surveillance; D012307:Risk Factors; D013036:Spasms, Infantile / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D014057:Tomography, X-Ray Computed