Isolation and thepay for congenital hypomyelinating disorders

• Project/Area Number: 23591264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Jichi Medical University (2013-2014); Kanagawa Cancer Center Research Institute (2011-2012)
• Principal Investigator: OSAKA Hitoshi 自治医科大学, 医学部, 教授 (90426320)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 白質形成不全 / POL3A / POL3B / HCAHC / 白質形成不全症 / PolIII

Outline of Final Research Achievements

1.We found gene that cause “Diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum”, HCAHC(New syndrome, proposed by Sasake et al.2009) Saitsu H, Osaka H, et al., Am J Hum Genet 89 (5):644-651.
2.We found phenotypic differences by POLR3A and POLR3B mutations. Takanashi JI, Osaka et al. Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations. Brain Dev. 2013 May 3. doi:pii: S0387-7604(13)00132-0.3.We proposed a geno-phenotypic correlation in Leukoencephalopathy Hypomyelinationwith Atrophy of the Basal Ganglia and Cerebellum. Kato M, Saitsu H, et al. Neurology. 2014 Jun 17;82(24):2230-7

Research Products

• [Journal Article] Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy. (2015)
  • Author(s): Kodera H, Osaka H, Iai M, Aida N, Yamashita A, Tsurusaki Y, Nakashima M, Miyake N, Saitsu H, Matsumoto N.
  • Journal Title: J Hum Genet. Volume: 60(2) Issue: 2 Pages: 97-101
  • DOI: 10.1038/jhg.2014.103
  • Peer Reviewed / Open Access
• [Journal Article] A Japanese girl with an early-infantile onset vanishing white matter disease resembling Cree leukoencephalopathy. (2014)
  • Author(s): Takano K, Tsuyusaki Y, Sato M, Takagi M, Anzai R, Okuda M, Iai M, Yamashita S,
  • Journal Title: Brain Dev. Volume: 37(6) Issue: 6 Pages: 638-42
  • DOI: 10.1016/j.braindev.2014.10.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expanding the phenotypic spectrum of TUBB4A-associated (2014)
  • Author(s): Miyatake S, Osaka H, Shiina M, Sasaki M, Takanashi J, Haginoya K, Wada T,
  • Journal Title: Neurology Volume: 82(24) Issue: 24 Pages: 2230-7
  • DOI: 10.1212/wnl.0000000000000535
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations. (2014)
  • Author(s): Takanashi JI, Osaka H, Saitsu H, et al.
  • Journal Title: Brain Dev. Volume: 89 Pages: 59-63
  • Peer Reviewed
• [Journal Article] Partial PLP1 Deletion Causing X-Linked Dominant Spastic Paraplegia Type 2. (2013)
  • Author(s): Matsufuji M, Osaka H, Gotoh L,et al
  • Journal Title: Pediatr Neurol. Volume: 49 Pages: 477-481
  • Peer Reviewed
• [Journal Article] A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia. (2013)
  • Author(s): 97. Kimura-Ohba S, Kagitani-Shimono K, Hashimoto N, Nabatame S, Okinaga T,Murakami A, Miyake N, Matsumoto N, Osaka H, Hojo K, Tomita R, Taniike M, Ozono K.
  • Journal Title: Am J Med Genet A. Volume: 161 Issue: 1 Pages: 203-7
  • DOI: 10.1002/ajmg.a.35686
  • Peer Reviewed
• [Journal Article] Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations. (2013)
  • Author(s): 98. Takanashi JI, Osaka H, Saitsu H, Sasaki M, Mori H, Shibayama H, Tanaka M,
  • Journal Title: Brain Dev. Volume: May 3 Issue: 3 Pages: 259-263
  • DOI: 10.1016/j.braindev.2013.03.006
  • Peer Reviewed
• [Journal Article] シンポジウム3, 先天性大脳白質形成不全症―疾患概念の確立から、病態解析・治療的展望まで2013；45：121ー特集・第54回日本小児神経学会総会 (2013)
  • Author(s): 小坂 仁、井上 健
  • Journal Title: 脳と発達 Volume: 45 Pages: 121-1
  • Peer Reviewed
• [Journal Article] 先天性大脳白質形成不全症の臨床症状と分子病態：シンポジウム3, 先天性大脳白質形成不全症―疾患概念の確立から、病態解析・治療的展望までー特集・第54回日本小児神経学会総会、 (2013)
  • Author(s): 小坂 仁、井上 健、才津 浩智
  • Journal Title: 脳と発達 Volume: 45 Pages: 127-31
  • Peer Reviewed
• [Journal Article] Paradoxical increase in seizure frequency with valproate in nonketotic hyperglycinemia. (2012)
  • Author(s): Tsuyusaki Y, Shimbo H, Wada T, Iai M, Tsuji M, Yamashita S, Aida N, Kure S, Osaka H
  • Journal Title: Brain Dev. Volume: 34 Pages: 72-75
  • NAID: 10031049636
  • Peer Reviewed
• [Journal Article] A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5 (2012)
  • Author(s): Saitsu H, Osaka H, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Matsumoto N
  • Journal Title: Brain Dev Volume: 34 Pages: 364-367
  • NAID: 10031050724
  • Peer Reviewed
• [Journal Article] Acute leukoencephalopathy possibly induced by phenytoin intoxication in an adult patient with methylenetetrahydrofolate reductase deficiency (2011)
  • Author(s): Arai M, Osaka H
  • Journal Title: Epilepsia Volume: 52 Issue: 7 Pages: 58-61
  • DOI: 10.1111/j.1528-1167.2011.03064.x
  • Peer Reviewed
• [Journal Article] Acute encephalopathy in a patient with Dravet syndrome. (2011)
  • Author(s): Tsuji M, Mazaki E, Ogiwara I, Wada T, Iai M, Okumura A, Yamashita S, Yamakawa K, Osaka H
  • Journal Title: Neuropediatrics Volume: 42 Issue: 02 Pages: 78-81
  • DOI: 10.1055/s-0031-1279725
  • Peer Reviewed
• [Journal Article] 5,10-Methylenetetrahydrofolate reductase deficiency with progressive polyneuropathy in an infant (2011)
  • Author(s): Tsuji M, Takagi A, Sameshima K, Iai M, Yamashita S, Shinbo H, Furuya N, Kurosawa K, Osaka H
  • Journal Title: Brain Dev Volume: 33 Pages: 521-524
  • NAID: 10029562192
  • Peer Reviewed
• [Journal Article] Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing. (2011)
  • Author(s): Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N
  • Journal Title: J Med Genet Volume: 48 Pages: 606-609
  • Peer Reviewed
• [Journal Article] Acute encephalopathy in two cases with severe congenital hydrocephalus (2011)
  • Author(s): Tanoue K, Matsui K, Ohshiro A, Yamamoto A, Hayashi T, Fujimoto J, Osaka
  • Journal Title: Brain Dev Volume: 33 Pages: 616-619
  • NAID: 10031121964
  • Peer Reviewed
• [Journal Article] A simple screening method using ion chromatography for the diagnosis of cerebral creatine deficiency syndromes (2011)
  • Author(s): Wada T, Shimbo H, Osaka H
  • Journal Title: Amino Acids Volume: on line Issue: 2 Pages: 993-997
  • DOI: 10.1007/s00726-011-1146-1
  • Peer Reviewed
• [Journal Article] Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2) (2011)
  • Author(s): Saitsu H, Osaka H, Sugiyama S, Kurosawa K, Mizuguchi T, Nishiyama K, Nishimura A, Tsurusaki Y, Doi H, Miyake N, Harada N, Kato M, Matsumoto N
  • Journal Title: Am J Med Genet A Volume: (in press) Issue: 1 Pages: 2879-84
  • DOI: 10.1002/ajmg.a.34363
  • Peer Reviewed
• [Journal Article] Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy (2011)
  • Author(s): Saitsu H, Osaka H, Sasaki M, Takanashi J, Hamada K, Yamashita A, Shibayama H, Shiina M, Kondo Y, Nishiyama K, Tsurusaki Y, Miyake N, Doi H, Ogata K, Inoue K, Matsumoto N
  • Journal Title: Am J Hum Genet Volume: 89 Pages: 644-651
  • Peer Reviewed
• [Presentation] ATG＞AGG (開始コドン)の変異で軽症の表現型を示したPelizaeus-Merzbacher病の一男児例 (2013)
  • Author(s): 山本亜矢子、大城亜希子、安西里恵、高木真理子、奥田美津子、新保裕子、高野亨子、和田敬仁、井合瑞江、山下純正、小坂 仁
  • Organizer: 第55回日本小児神経学会
  • Place of Presentation: 大分
• [Presentation] 先天性大脳白質形成不全症の臨床症状と分子病態；シンポジウム (2012)
  • Author(s): 小坂仁1), 井上健2), 才津浩智3) 1)神奈川県立こども医療センター神経内科, 2)国立精神・神経医療研究センター神経研究所疾病研究第2部, 3)横浜市立大学医学部遺伝学教室
  • Organizer: 第54回日本小児神経学会総会
  • Place of Presentation: 札幌
• [Presentation] 先天性大脳白質形成不全症：ゲノム解析から診断, 治療への取り組み；シンポジウム (2012)
  • Author(s): 井上健1), 岩城明子2), 黒澤健司3), 高梨潤一4), 出口貴美子1), 山本俊至5), 小坂仁6)
  • Organizer: 第54回日本小児神経学会総会
  • Place of Presentation: 札幌
• [Presentation] A SOX10 binding site mutation in GJC2 promoter causes Pelizaeus-Merzbacher-like disease (2011)
  • Author(s): Hitoshi Osaka, Atsuo Nezu, Hirotomo Saitsu,Kenji Kurosawa,Hiroko Shimbo, Naomichi Matsumoto,Ken Inoue,A
  • Organizer: 第53回日本小児神経学会総会 English session
  • Place of Presentation: yokohama