Development of genetically engineered animal models and novel therapeutic measures for human Epilepsy

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249062
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Fukuoka University
• Principal Investigator: HIROSE Shinichi 福岡大学, 医学部, 教授 (60248515)
• Co-Investigator(Renkei-kenkyūsha): MISUMI Yoshio 福岡大学, 医学部, 准教授 (10148877) ; TAKANO Yukio 福岡大学, 薬学部, 教授 (50113246) ; SAITO Ryo 福岡大学, 薬学部, 講師 (80122696) ; DESHIMARU Masanobu 福岡大学, 理学部, 准教授 (70309889) ; INOUE Ryuji 福岡大学, 医学部, 教授 (30232573) ; KATSURABAYASHI Shutaro 福岡大学, 薬学部, 助教 (50435145) ; ARAKI Kimi 熊本大学, 准教授 (90211705)
• Project Period (FY): 2009 – 2011
• Keywords: 小児神経学

Research Abstract

We have identified over 100 genetic abnormalities which cause epilepsy in our DNA bank. We have also successfully genetically engineered mice which harbor genetic abnormalities identified in human. These outcomes have established a system which allows rapid and continuous identification and analyses of genetic abnormalities in individuals with epilepsy. Now novel therapeutic measures based upon the pathogeneses of epilepsy are being developed.

Research Products

• [Journal Article] A Novel Mutation of Human Liver Alanine:Glyoxylate Aminotransferase Causes Primary Hyperoxaluria Type 1:Immunohistochemical Quantification and Subcellular Distribution. (2012)
  • Author(s): Kawai C, Minatogawa Y, Akiyoshi H, Hirose S, Suehiro T, Tone S
  • Journal Title: Acta Histochem. cytochem. Volume: 45((2)) Pages: 121-9
  • DOI: doi:10.1267/ahc.11042
  • Peer Reviewed
• [Journal Article] On the likelihood of SCN1A microdeletions or duplications in Dravet syndrome withmissense mutation (2012)
  • Author(s): Shi X, Wang J, Kurahashi H, Ishii A, Higurashi N, Kaneko S, Hirose S
  • Journal Title: Brain Dev Volume: 99 Pages: 27-38
  • Peer Reviewed
• [Journal Article] Mutation of the SCN1A gene in acute encephalophathy (2012)
  • Author(s): Saitoh M, Shinohara M, Hoshino H, Kubota M, Amemiya K, Takanashi J, Hirose S, Mizuguchi M
  • Journal Title: Epilepsia Pages: 1-7
  • DOI: doi:10.1111/j.1528-1167.2011.03402.x
  • Peer Reviewed
• [Journal Article] Mutations in PRRT2 responsible for paroxysmal kinesigenic dyskinesias also cause benign familialinfantile convulsions. (2012)
  • Author(s): Ono S, Yoshiura K , KinoshitaA, Kikuchi T, Nakane Y, Kato N,Sadamatsu M , Konishi T , Nagamitsu S , Matsuura M, Yasuda A, KomineM, Kanai K , Inoue T , Osamura T , Saito K , Hirose S, Koide H, Tomita H , Ozawa H , Niikawa N and Kurotaki N.
  • Journal Title: J Hum Genet Pages: 1-4
  • DOI: doi:10.1038/jhg.2012.23
  • Peer Reviewed
• [Journal Article] PCDH19 Mutation in Japanese Females with Epilepsy (2012)
  • Author(s): Higurashi N, Shi X, Yasumoto S, Oguni K, Itomi K, Miyamoto A, Shirishi H, Kato T, Makita Y, Hirose S.
  • Journal Title: Epilepsy Res Volume: 99 Pages: 28-37
  • DOI: DOI:10.1016/j.eplepsyres.2011.10.014
  • Peer Reviewed
• [Journal Article] Clinical spectrum of SCN2A mutations (2011)
  • Author(s): Shi X, Yasumoto S, Kurahashi K,Nakagawa E, Fukasawa T, Uchiya S, Hirose S
  • Journal Title: Brain Dev Volume: 34(7) Pages: 541-5
  • DOI: doi:10.1016/j.braindev.2011.09.016
  • Peer Reviewed
• [Journal Article] Early-onset absence epilepsy at eight months of age (2011)
  • Author(s): Kobayashi Y, Akasaka N, Ohashi T, SaitohS, Tomonoh Y, Hirose S, Tohyama J
  • Journal Title: Epileptic Disord. Volume: 13(4) Pages: 417-21
  • Peer Reviewed
• [Journal Article] Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation. (2011)
  • Author(s): Hwang SK, Makita Y, Kurahashi H, Cho YW, Hirose S
  • Journal Title: J Hum Genet Volume: 56(8) Pages: 609-12
  • DOI: doi:10.1111/j.1528-1167.2011.03002.x
  • Peer Reviewed
• [Journal Article] Mortality in Dravet syndrome: search for risk factors in Japanese patients (2011)
  • Author(s): Sakauchi M, Oguni H, Kato I, Osawa M, Hirose S, Kaneko S, Takahashi Y, Takayama R, Fujiwara T
  • Journal Title: Epilepsia. Volume: 52 Suppl 2 Pages: 50-4
  • DOI: doi:10.1111/j.1528-1167.2011.03002.x
  • Peer Reviewed
• [Journal Article] Diagnosing nocturnal frontal lobe epilepsy: A case study of two children (2011)
  • Author(s): Tomonoh Y, Yasumoto S, Ihara Y, Fujita T, Nakamura N, Ninomiya S, Kodama R, Ideguchi H, Inoue T, Mitsudome A, Hirose S
  • Journal Title: Seizure Volume: 20(7) Pages: 583-5.
  • DOI: doi:10.1016/j.seizure.2011.03.004
  • Peer Reviewed
• [Journal Article] The Developmental Changes of Na(v)1.1 and Na(v)1.2 Expression in the Human Hippocampus and Temporal Lobe. (2011)
  • Author(s): Wang W, Takashima S, Segawa Y, Itoh M, Shi X, Hwang SK, Nabeshima K, Takeshita M, Hirose S.
  • Journal Title: Brain Res Volume: 1389(5) Pages: 61-70
  • DOI: doi:10.1016/j.brainres.2011.02.083
  • Peer Reviewed
• [Journal Article] A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency (2011)
  • Author(s): Yamakawa Y, Nakazawa T, Ishida A, Saito N, Komatsu M, Matsubara T, Obinata K, Hirose S, Okumura A, Shimizu T.
  • Journal Title: Brain Dev Volume: 34(2) Pages: 107-12
  • DOI: doi:10.1016/j.braindev.2011.05.003
  • Peer Reviewed
• [Journal Article] Positive association between benign familial infantile convulsions and LGI4 (2010)
  • Author(s): Ishii A, Zhang B, Kaneko S, Hirose S
  • Journal Title: Brain Dev Volume: 32 Pages: 538-43
  • DOI: doi:10.1016/j.braindev.2009.09.006
  • Peer Reviewed
• [Journal Article] Genetic testing in the epilepsies (2010)
  • Author(s): Ottman R, Hirose S
  • Journal Title: Report of the ILAE Genetics Commission Epilepsia Volume: 51(4) Pages: 655-670
  • DOI: doi:10.1111/j.1528-1167.2009.02429.x
  • Peer Reviewed
• [Journal Article] IgG subclasses and complement pathway in segmental and global membranous nephropathy (2010)
  • Author(s): Segawa Y, Hisano S, Matsushita M, Fujita T, Hirose S, Takeshita M, Iwasaki H
  • Journal Title: Pediatr Nephrol Volume: 25(6) Pages: 1091-9
  • DOI: doi:10.1007/s00467-009-1439-8
  • Peer Reviewed
• [Journal Article] Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies (2010)
  • Author(s): Shi X, Huang MC, Ishii A, Yoshida S, Okada M, Morita K, Nagafuji H, Yasumoto S, Kaneko S, Kojima T, Hirose S.
  • Journal Title: J Hum Genet Volume: 55(6) Pages: 375-8.
  • DOI: doi:10.1038/jhg.2010.47
  • Peer Reviewed
• [Journal Article] Interaction of golgin-84 with the conserved oligomeric Golgi (COG)complex mediates the intra-Golgi retrograde transport. (2010)
  • Author(s): Sohda M, Misumi Y, Yamamoto A, Nakamura N, Ogata S, Sakisaka S, Hirose S, Ikehara Y, Oda K
  • Journal Title: Traffic Volume: 11 Pages: 1552-66
  • DOI: doi:10.1111/j.1600-0854.2010.01123.x
  • Peer Reviewed
• [Journal Article] Clinical features of Wilson disease: Analysis of 10 cases (2010)
  • Author(s): Takeyama Y, Yokoyama K, Takata K, Tanaka T, Sakurai K, Matsumoto T, Iwashita H, Ueda S, Hirano G, Hanano T, Nakane H, Morihara D, Nishizawa S, Yoshikane M, Anan A, Kakumitsu S, Kitamura Y, Sakamoto M, Irie M, Iwata K,Shakado S, Sohda T, Watanabe H, Hirose S, Hayashi H, Noritomi T, Yamashita Y, Sakisaka S.
  • Journal Title: Hepatol Res Volume: 40(12) Pages: 1204-11.
  • DOI: doi:10.1111/j.1872-034X.2010.00728.x
  • Peer Reviewed
• [Journal Article] Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in FukuokaPrefecture (2010)
  • Author(s): Torisu H, Kira R, Ishizaki Y, Sanefuji M, Yamaguchi Y, Yasumoto S, Murakami Y, Shimono M, Nagamitsu S, Masuzaki M, Amamoto M, Kondo R, Uozumi T, Aibe M, Gondo K, Hanai T, Hirose S, Matsuishi T, Shirahata A, Mitsudome A, Hara T.
  • Journal Title: Japan. Brain Dev Volume: 32(6) Pages: 454-62
  • DOI: doi:10.1016/j.braindev.2009.10.006
  • Peer Reviewed
• [Journal Article] Benign convulsions with mild gastroenteritis: is it associated with sodium channel geneSCN1A mutation? (2010)
  • Author(s): Weng WC, Hirose S, Lee WT
  • Journal Title: J Child Neurol Volume: 25(12) Pages: 1521-4
  • DOI: DOI:10.1177/0883073810370898
  • Peer Reviewed
• [Journal Article] Current Proceedings of Febrile Seizures and Related Epileptic Syndromes in SCN1A: from Bedside toBench. (2009)
  • Author(s): Chen S-J, Hirose S
  • Journal Title: J Med Sci Volume: 29(4) Pages: 167-72
  • Peer Reviewed
• [Journal Article] A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions (2009)
  • Author(s): Ishii A, Fukuma G, Uehara A, Miyajima T, Makita Y, Hamachi A, Yasukochi M, Inoue T, Yasumoto S, Okada M, Kaneko S, Mitsudome A, Hirose S.
  • Journal Title: Brain Dev Volume: 31(1) Pages: 27-33
  • DOI: doi:10.1016/j.braindev.2008.05.010
  • Peer Reviewed
• [Journal Article] Physicochemical property changes of amino acid residues that accompany missense mutations in SCN1A affect epilepsyphenotype severity. (2009)
  • Author(s): Kanai K, Yoshida S, Hirose S, Oguni H, Kuwabara S, Sawai S, Hiraga A, Fukuma G, Iwasa H, Kojima T, Kaneko S.
  • Journal Title: J Med Genet. Volume: 46(10) Pages: 671-9
  • DOI: doi:10.1136/jmg.2008.060897
  • Peer Reviewed
• [Journal Article] Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy with febrile seizures plus. (2009)
  • Author(s): Kumakura A, Ito M, Hata D, Oh N, Kurahashi H, Wang JW, Hirose S
  • Journal Title: Brain Dev Volume: 31(2) Pages: 179-82
  • DOI: doi:10.1016/j.braindev.2008.06.001
  • Peer Reviewed
• [Journal Article] Deletions involving both KCNQ2 and CHRNA4 present with benign familial neonatalseizures (2009)
  • Author(s): Kurahashi H, Wang JW, Ishii A, Kojima T, Wakai S, Kizawa T, Fujimoto Y, Kikkawa K, Yoshimura K, Inoue T, Yasumoto S, Ogawa A, Kaneko S, Hirose S.
  • Journal Title: Neurology Volume: 73(15) Pages: 1214-7
  • Peer Reviewed
• [Journal Article] Hemiconvulsion-hemiplegia syndrome in a patient with severe myoclonic epilepsy in infancy. (2009)
  • Author(s): Sakakibara T, Nakagawa E, Saito Y, Sakuma H, Komaki H, Sugai K, Sasaki M, Kurahashi H, Hirose S.
  • Journal Title: Epilepsia Volume: 50(9) Pages: 2158-62
  • DOI: doi:10.1111/j.1528-1167.2009.02175.x
  • Peer Reviewed
• [Journal Article] Missense mutation of the sodium channel gene SCN2A causes Dravet syndrome (2009)
  • Author(s): Shi X, Yasumoto S, Nakagawa E, Fukasawa T, Uchiya S, Hirose S
  • Journal Title: BrainDev Volume: 31 Pages: 758-62
  • DOI: doi:10.1016/j.braindev.2009.08.009
  • Peer Reviewed
• [Journal Article] Lack of potassium current in W309R mutant KCNQ3 channel causing benign familial neonatalconvulsions (BFNC). (2009)
  • Author(s): Sugiura Y, Nakatsu F, Hiroyasu K, Ishii A, Hirose S, Okada M, Jibiki I, Ohno H, Kaneko S, Ugawa Y.
  • Journal Title: Epilepsy Res Volume: 84(1) Pages: 82-5
  • DOI: doi:10.1016/j.eplepsyres.2008.12.003
  • Peer Reviewed
• [Journal Article] Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome
  • Author(s): Sakauchi M,Oguni H, Kato I, Osawa M, Hirose S, Kaneko S, Takahashi Y, Takayama R, Fujiwara T
  • Journal Title: Epilepsia Volume: 52(6) Pages: 1144-9
  • DOI: doi:10.1111/j.1528-1167.2011.03053.x
  • Peer Reviewed
• [Presentation] Complications in a metachromatic leukodystrophy(MLD) patient's long-term-follow up:neurologic complications./ Takahito Inoue (2010)
  • Author(s): Michitaka Yonekura, Takako Fujita, Yukiko Ihara, Yuko Tomonoh, Hitoshi Ideguchi, Sawa Yasumoto, Shiho Kodama, Shinichi Hirose.
  • Organizer: The 1st Asian Congress for Inherited Metabolic Diseases
  • Place of Presentation: 福岡
  • Year and Date: 20100307-10
• [Presentation] The Neurological prognosis of organic academia (2010)
  • Author(s): Takako Fujita, Yukiko Ihara, yuko Tomonoh, Shinya Ninomiya, Yurie Kodama, Hitoshi Ideguchi, Takahito Inoue, Sawa Yasumoto, Shinichi Hirose
  • Organizer: The 1st Asian Congress for InheritedMetabolic Diseases
  • Place of Presentation: 福岡
  • Year and Date: 20100307-10
• [Presentation] A Neuronal Ceroid-Lipofuscinosis case with Epilepsy and Sick Sinus Syndrome (2010)
  • Author(s): Yukiko Ihara, Yuko Tomonoh, Takako Fujita, Hiroshi Ideguchi, Takahito Inoue, Sawa Yasumoto, Shinichi Hirose
  • Organizer: The 1st Asian Congress for Inherited Metabolic Diseases
  • Place of Presentation: 福岡
  • Year and Date: 20100307-10
• [Presentation] Progressive mycolonus epilepsy due to Gaucher disease type 3 without hepatosplenomegaly (2010)
  • Author(s): Norimichi Higurashi, Shin-ichiro Hamano, Asako Tajima, Toya Ohashi, Hiroyuki Ide, Shinichi hirose
  • Organizer: The 1st Asian Congressfor Inherited Metabolic Diseases
  • Place of Presentation: 福岡
  • Year and Date: 20100307-10
• [Presentation] てんかん遺伝子研究の進歩とその臨床応用 (2010)
  • Author(s): 廣瀬伸一
  • Organizer: 南大阪小児疾患研究会
  • Place of Presentation: 大阪
  • Year and Date: 2010-02-06
• [Presentation] Genetics of febrile Serizures and Related Conditions (2009)
  • Author(s): Hirose S
  • Organizer: 10th Asian & Oseanian Cogress of Child Nuerology
  • Place of Presentation: Korea
  • Year and Date: 20090610-13
• [Presentation] てんかんの遺伝子研究の進歩とその臨床応用 (2009)
  • Author(s): 廣瀬伸一
  • Organizer: 第21回山梨神経学研究会学術講演会
  • Place of Presentation: 山梨
  • Year and Date: 2009-06-02
• [Remarks]
  • URL: http://www.med.fukuoka-u.ac.jp/epilepsy/
• [Patent(Industrial Property Rights)] 注意欠陥/多動性障害モデル非ヒト哺乳動物 (2009)
  • Inventor(s): 廣瀬伸 一 、高崎浩太郎
  • Industrial Property Rights Holder: 福岡大学
  • Industrial Property Number: 特許,特願 2009-188152
  • Filing Date: 2009-08-14