Common genes and recurrent causative variants in 957 Asian patients with pediatric epilepsy

Author:

Kim Se Hee12ORCID,Seo Jieun3ORCID,Kwon Soon Sung3,Teng Lip‐Yuen4ORCID,Won DongJu3,Shin Saeam3,Lee Joon Soo12ORCID,Lee Seung‐Tae3ORCID,Choi Jong Rak3ORCID,Kang Hoon‐Chul12ORCID

Affiliation:

1. Division of Pediatric Neurology, Epilepsy Research Institute, Severance Children's Hospital Yonsei University College of Medicine Seoul South Korea

2. Department of Pediatrics, Yonsei University College of Medicine Severance Children's Hospital Seoul South Korea

3. Department of Laboratory Medicine, Severance Hospital Yonsei University College of Medicine Seoul South Korea

4. Pediatric Neurology Unit, Department of Pediatrics Hospital Tunku Azizah Kuala Lumpur Malaysia

Abstract

AbstractObjectiveWe aimed to identify common genes and recurrent causative variants in a large group of Asian patients with different epilepsy syndromes and subgroups.MethodsPatients with unexplained pediatric‐onset epilepsy were identified from the in‐house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records.ResultsOf the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53–9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic‐atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3).SignificanceHere we present the results of a large‐scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities.

Funder

Yonsei University College of Medicine

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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