Research of early diagnosis system for epileptic encephalopathy by whole exome sequencing

• Project/Area Number: 16K19626
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Yamagata University
• Principal Investigator: Nakamura Kazuyuki 山形大学, 医学部, 助教 (20436215)
• Research Collaborator: KATO Mitsuhiro 昭和大学, 医学部, 小児科 ; MATSUMOTO Naomichi 横浜市立大学, 医学研究科遺伝学
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 小児神経疾患 / てんかん / 知的障害 / てんかん性脳症 / 全エクソン解析 / 急性脳症 / HECW2 / 脳形成異常症 / 脳・神経 / ゲノム

Outline of Final Research Achievements

Pediatric neurological diseases such as epileptic encephalopathy often have poor neurological prognosis. We thought that establishing an early diagnosis system is important while clarifying its genetic background. In this study, we identified a novel mutation of the KCNQ3 gene in West syndrome. Secondly, we confirmed the CPT2 polymorphism in acute encephalopathy. Thirdly, we found HECW2 mutation in patient with attacks of flaccid paralysis. We need elucidate the functions of these genes, develop for order-made therapy and shorten the time for analysis.

Research Products

• [Journal Article] Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder (2018)
  • Author(s): Takata A, Miyake N, Tsurusaki Y, Fukai R, Miyatake S, Koshimizu E, Kushima I, Okada T, ...Matsumoto N.
  • Journal Title: Cell Reports Volume: 22(3) Issue: 3 Pages: 734-747
  • DOI: 10.1016/j.celrep.2017.12.074
  • Peer Reviewed / Open Access
• [Journal Article] 新たなDCX遺伝子ミスセンス変異を認めた滑脳症の男児例 (2017)
  • Author(s): 渡邊あさみ，徳田桐子，楠目和代，福田光成，中村和幸，加藤光広，石井榮一
  • Journal Title: 愛媛医学 Volume: 36(3) Pages: 167-170
  • Peer Reviewed
• [Journal Article] Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia (2016)
  • Author(s): Makrythanasis P, Kato M, Zaki MS, Saitsu H, Nakamura K, Santoni FA, Miyatake S, Nakashima M, Issa MY, Guipponi M, Letourneau A, Logan CV, Roberts N, Parry DA, Johnson CA, Matsumoto N, Hamamy H, Sheridan E, Kinoshita T, Antonarakis SE, Murakami Y.
  • Journal Title: Am J Hum Genet Volume: 98 Issue: 4 Pages: 615-626
  • DOI: 10.1016/j.ajhg.2016.02.007
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Novel GPI deficiency caused by PIGG mutations shows intellectual disability, seizures and hypotonia (2017)
  • Author(s): 1)Nakamura K, Kato M, Makrythanasis P, Zaki M, Saitsu H, Santoni F, Miyatake S, Nakashima M, Matsumoto N, Hamamy H, Sheridan E, Kinoshita T, Antonarakis SE, Murakami Y
  • Organizer: 15th Asian and Oceania Congress of Child Neurology
  • Int'l Joint Research
• [Presentation] First case report on West syndrome with a de novo KCNQ3 mutation (2017)
  • Author(s): Nakamura K, Yokoyama J, Abe A, Saitsu H, Nakashima M, Matsumoto N, Kato M
  • Organizer: 32nd International Epilepsy Congress
  • Int'l Joint Research
• [Presentation] Novel GPI deficiency caused by PIGG mutations shows intellectual disability, seizures and hypotonia (2016)
  • Author(s): Kazuyuki Nakamura, Mitsuhiro Kato, Periklis Makrythanasis, Maha Zaki, Hirotomo Saitsu, Federico Santoni, Satoko Miyatake, Mitsuko Nakashima, Naomichi Matsumoto, Hanan Hamamy, Eamonn Sheridan, Taroh Kinoshita, Stylianos E Antonarakis, Yoshiko Murakami
  • Organizer: 第58回日本小児神経学会学術集会
  • Place of Presentation: 京王プラザホテル 新宿
  • Year and Date: 2016-06-03