Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing

• DOI: 10.1186/s12920-018-0320-7
• Publication Date: 2018-02-01T07:46:45Z
• Authors: John Hoon Rim; Se Hee Kim; In Sik Hwang; Soon Sung Kwon; Jieun Kim; Hyun Woo Kim; Min Jung Cho; Ara Ko; Song Ee Youn; Jihun Kim; Young Mock Lee; Hee Jung Chung; Joon Soo Lee; Heung Dong Kim; Jong Rak Choi; Seung-Tae Lee; Hoon-Chul Kang
• Keywords: Medical genetics; Human genetics

We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing diagnosis rate. assessed 74 EOE whose seizures started before 3 years age customized NGS that included 172 genes. Single nucleotide variants (SNVs) exonic chromosomal copy number variations (CNVs) were intensively examined our pipeline crosschecked commercial or pre-built software. Variants filtered prioritized in-depth clinical review, finally classified according American College Medical Genetics Genomics guidelines. Each case was further discussed monthly consensus meeting participation all laboratory personnel, bioinformaticians, geneticists, clinicians. The identified 28 (37.8%) genetic abnormalities; 25 had pathogenic likely SNVs 17 genes including SXTBP1 (n = 3), CDKL5 2), KCNQ2 SCN1A SYNGAP1 GNAO1 KCNT1 BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 1). other CNVs (2 duplications 1 deletion) varying sizes (from 2.5 Mb 12 Mb). overall yield 37.8% after following step-by-step approach consensus. is useful tool great EOE. Diagnostic yields can be maximized standardized team-based approach.