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01-03-2017 | Original Article

Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy

Authors: Sarenur Gokben, Huseyin Onay, Sanem Yilmaz, Tahir Atik, Gul Serdaroglu, Hande Tekin, Ferda Ozkinay

Published in: Acta Neurologica Belgica | Issue 1/2017

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.

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Title: Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy
Authors: Sarenur Gokben
Huseyin Onay
Sanem Yilmaz
Tahir Atik
Gul Serdaroglu
Hande Tekin
Ferda Ozkinay
Publication date: 01-03-2017
Publisher: Springer International Publishing
Published in: Acta Neurologica Belgica / Issue 1/2017
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI: https://doi.org/10.1007/s13760-016-0709-z

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Targeted next generation sequencing: the diagnostic value in early-onset epileptic encephalopathy

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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