Abstract
Background: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. Methods: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians. Results: The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus. Conclusions: NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.
| Original language | English |
|---|---|
| Article number | 6 |
| Journal | BMC Medical Genomics |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2018 Feb 1 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
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Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing. / Rim, John Hoon; Kim, Se Hee; Hwang, In Sik; Kwon, Soon Sung; Kim, Jieun; Kim, Hyun Woo; Cho, Min Jung; Ko, Ara; Youn, Song Ee; Kim, Jihun; Lee, Young Mock; Chung, Hee Jung; Lee, Joon Soo; Kim, HeungDong; Choi, Jong Rak; Lee, Seung Tae; kang, hoonchul.
In: BMC Medical Genomics, Vol. 11, No. 1, 6, 01.02.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing
AU - Rim, John Hoon
AU - Kim, Se Hee
AU - Hwang, In Sik
AU - Kwon, Soon Sung
AU - Kim, Jieun
AU - Kim, Hyun Woo
AU - Cho, Min Jung
AU - Ko, Ara
AU - Youn, Song Ee
AU - Kim, Jihun
AU - Lee, Young Mock
AU - Chung, Hee Jung
AU - Lee, Joon Soo
AU - Kim, HeungDong
AU - Choi, Jong Rak
AU - Lee, Seung Tae
AU - kang, hoonchul
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Background: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. Methods: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians. Results: The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus. Conclusions: NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.
AB - Background: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. Methods: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians. Results: The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus. Conclusions: NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.
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U2 - 10.1186/s12920-018-0320-7
DO - 10.1186/s12920-018-0320-7
M3 - Article
C2 - 29390993
VL - 11
JO - BMC Medical Genomics
JF - BMC Medical Genomics
SN - 1755-8794
IS - 1
M1 - 6
ER -