• 1 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • 2 Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan
  • 3 Pediatric Neurology Department Pediatric Epilepsy Service, Assaf Harofeh Medical Center, Zerifin, Israel
  • 4 Department of Neurology, Miyagi Children's Hospital, Sendai, Japan
  • 5 Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • 6 Department of Pediatrics, JA Toride General Hospital, Toride, Ibaraki, Japan
  • 7 Department of Pediatrics, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan
  • 8 Division of Neurology, National Center for Child Health and Development, Tokyo, Japan
  • 9 Division of Neurology, Saitama Children's Medical Center, Saitama, Japan
  • 10 Neurogenetics Unit, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
  • 11 Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia
  • 12 Genetic Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  • 13 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • 14 Epilepsy Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
  • 15 Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • 16 Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan
Clin. Genet., 2018 03;93(3):577-587.
PMID: 28940419 DOI: 10.1111/cge.13144


Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.