An exploration of causative genes of focal cortical dysplasia with intractable epilepsy, using advanced technologies

2012 Fiscal Year Final Research Report

• Project/Area Number: 22659197
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: ITO Masayuki 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 室長 (50243407)
• Project Period (FY): 2010 – 2012
• Keywords: 難治性てんかん / 大脳皮質異形成 / 遺伝子

Research Abstract

Intractable epilepsy in childhood has other problems and leads to be difficult to spend daily ability. The major cause of the epilepsy is focal cortical dysplasia (FCD), which shows characteristic dysplasia in a part of cerebral cortex. In the present study, we explore causative genes of FCD formation, using cell sorting technique and CGH （Comparative genomic hybridization）array analysis. We used DNA samples of 4 FCD patients, whose parents agreed with the research usage under an informed consent. As a result, we obtained no 4-patient common abnormal gene, two 3-patient common abnormal genes and thirteen 2-patient common abnormal genes. Among them, we could pick up six genes for the candidates. We advance further analyses for the goal.

Research Products

• [Journal Article] A case of severe progressive early-onset epileptic encephalopathy: unique GABAergic interneuron distribution and imagings (2013)
  • Author(s): Inoue T, Kawawakia H, Kuki I, Nabatame S, Tomonoh Y, Sukigara S, Horino A, Nukui M, Okazaki S, Tomiwa K, Kimura-Ohba S, Inoue T, Hirose S, Shiomi M, Itoh M.
  • Journal Title: J Neurol Sci Volume: 327 Pages: 65-72
  • DOI: doi:10.1016/j.jns.2013.01.038.
  • Peer Reviewed
• [Journal Article] Hypoalbuminemia in early-onset dentatorubralpallidoluysian atrophy due to leakage of albumin in multiple organs (2013)
  • Author(s): Nagai S, Saito Y, Endo Y, Saito T, Kenji Sugai K, Ishiyama A, Komaki H, Nakagawa E, Sasaki M, Ito K, Saito Y, Sukigara S, Ito M, Goto Y, Ito S, Matsuoka K
  • Journal Title: J Neurol Volume: 260 Pages: 1263-1271
  • DOI: doi:10.1007/s00415-012-6787-9.
  • Peer Reviewed
• [Journal Article] Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation: unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly (2012)
  • Author(s): Arai A, Saito T, Hanai S, Otsuki T, Nakagawa E, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sugai K, Sasaki M, Goto Y, Itoh M
  • Journal Title: Brain Res Volume: 1470 Pages: 89-97
  • DOI: doi: 10.1016/j. brainres.2012.06.009.
  • Peer Reviewed
• [Journal Article] Imbalance of interneuron distribution between neocortex and basal ganglia: Consideration of epileptogenesis of focal cortical dysplasia (2012)
  • Author(s): Sakakibara T, Sukigara S, Otsuki T, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sato N, Nakagawa E, Sugai K, Sasaki M, Goto Y, Itoh M
  • Journal Title: J Neurol Sci Volume: 323 Pages: 128-133
  • DOI: doi: 10.1016/j.jns.2012.08. 035.
  • Peer Reviewed
• [Journal Article] Delayed maturation of neurons of focal cortical dysplasia IIA and IIB: consideration from specific neocortical-layer marker expression (2012)
  • Author(s): Sakakibara T, Saito T, Otsuk T, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sato N, Nakagawa E, Sugai K, Sasaki M, Goto Y, Itoh M
  • Journal Title: J Neuropathol Exp Neurol 2012 Volume: 71(8) Pages: 741-749
  • DOI: DOI: 10.1097/NEN.0b013e 318262e41a
  • Peer Reviewed
• [Journal Article] Methyl CpG-binding protein isoform MeCP2_e2 is dispensable for phenotypes but essential for embryo viability and placenta development (2012)
  • Author(s): Itoh M, Tahimic CGT, Ide S, Otsuki A, Sasaoka T, Noguchi S, Oshimura M, Goto Y, Kurimasa A
  • Journal Title: J Biol Chem 2012 Volume: 287(17) Pages: 13859-13867
  • DOI: doi:10.1074/jbc.M111.309864.
  • Peer Reviewed
• [Journal Article] Progressive leukoencephalopathy with intracranial calcification, congenital deafness and developmental deterioration (2011)
  • Author(s): Kuki I, Kawawaki H, Okazaki S, Kimura S, Nakano T, Fukushima H, Inoue T, Tomiwa K, Itoh M
  • Journal Title: Am J Med Genet A 2011 Volume: 155 Pages: 2832-2837
  • DOI: doi: 10.1002/ajmg.a.34256.
  • Peer Reviewed
• [Journal Article] Neocortical layer-formation of the human developing brains and lissencephalies: consideration of layer-specific markers expression (2010)
  • Author(s): Saito T, Hanai S, Takashima S, Nakagawa E, Okazaki S, Inoue T, Miyata R, Hoshino K, Akashi T, Sasaki M, Goto Y, Hayashi M, Itoh M
  • Journal Title: Cereb Cortex 2011 Volume: 21 Pages: 588-596
  • DOI: doi:10.1093/cercor/bhq125.
  • Peer Reviewed
• [Journal Article] Abnormal development of neurons in focal cortical dysplasia: neuronal mis-maturation from an immunohistochemical consideration (2010)
  • Author(s): Hanai S, Saito T, Nakagawa E, Arai A, Otsuki T, Sasaki M, Goto Y, Itoh M
  • Journal Title: Seizure 2010 Volume: 19 Pages: 274-279
  • DOI: doi: 10.1016/j.seizure.2010.04.003.
  • Peer Reviewed
• [Presentation] GABAergic interneuron pathology: ARX normal development and its mutation (2012)
  • Author(s): Itoh M, Inage Y, Kitamura K, Goto Y, Halliday WC
  • Organizer: The 10th European Congress of Neuropathology
  • Place of Presentation: Edingburgh, UK
  • Year and Date: 20120605-09
• [Presentation] GABAergic interneurons lead to the epileptogenesis: Interneuron pathology associated with ARX mutation (2012)
  • Author(s): Itoh M, Okazaki S, Kawawaki H, Inoue T, Goto Y
  • Organizer: Symposium 1, Basic Science. The 10th European Congress on Epileptology
  • Place of Presentation: London, UK
  • Year and Date: 2012-10-01
• [Presentation] Abnormal maturation of non-dysmorphic neurons in focal cortical dysplasia: immunohistochemical considerations (2011)
  • Author(s): Itoh M, Hanai S, Saito T, Nakagawa E, Sasaki M, Otsuki T, Goto Y
  • Organizer: The 29th International Epilepsy Congress
  • Place of Presentation: Rome, Italy
  • Year and Date: 20110828-0901
• [Presentation] Defferent pathophysiology of focal cortical dysplasia IIA and IIB: specific neocortical-layer marker expression (2011)
  • Author(s): Sakakibara T, Saito T, Otsuki T, Takahashi A, Kaneko Y, Kaido T, Saito Y, Nakagawa E, Sugai K, Sasaki K, Goto Y, Itoh M
  • Organizer: The 29th International Epilepsy Congress
  • Place of Presentation: Rome, Italy
  • Year and Date: 20110828-0901
• [Presentation] ARX contributes to development and differentiation of endocrine cells in human pancreas (2011)
  • Author(s): Itoh M, Okazaki S, Miyata R, Inoue T, Masaharu Hayashi M, Goto Y
  • Organizer: The 93rd Annual Meeting & Expo
  • Place of Presentation: Boston, USA
  • Year and Date: 20110604-07
• [Presentation] Neocortical Layer-formation of Human Developing brains and lissencephalies: Consideration of layer-specific marker expression (2010)
  • Author(s): Saito T, Okazaki S, Inoue T, Sasaki M, Goto Y, Hayashi M, Itoh M
  • Organizer: The 17th International Congress of Neuropathology
  • Place of Presentation: Salzburg, Austria
  • Year and Date: 20100911-15
• [Book] てんかんの病理. 最新医学 別冊. 新しい診断と治療のABC 74. てん かん (2012)
  • Author(s): 伊藤雅之
  • Total Pages: 72-82
  • Publisher: 最新医学社
• [Book] 急性脳症の病理. 小児科臨床ピクシス28 急性脳炎・脳症 (2011)
  • Author(s): 伊藤雅之
  • Total Pages: 16-21
  • Publisher: 中山書店