Elucidation for genetic basis and molecular pathology of infantile epileptic encephalopathy

• Project/Area Number: 16H05160
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Saitsu Hirotomo 浜松医科大学, 医学部, 教授 (40402838)
• Research Collaborator: SHIBASAKI kaori
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: てんかん性脳症 / 新規責任遺伝子 / エクソーム解析 / マウスモデル / 全エクソーム解析 / ゲノム / 遺伝子解析 / てんかん / 変異ノックインマウス / 遺伝子変異 / 乳児てんかん / 細胞モデル

Outline of Final Research Achievements

We identified genetic abnormalities in more than 50% of cases of infantile epileptic encephalopathies by comprehensive gene mutation analysis and copy number variation detection system using whole exome sequencing data. In addition, PPP2R1A, CACNA1G, CSNK2A1, and GABRB2 are identified as novel candidate genes through combining gene mutation data in other large-scale cohorts of brain and nervous diseases and in our study. Furthermore, we identified SLC12A5, CNPY3, CYFIP2 and RHOBTB2 as novel causative genes and reported them together with functional findings in their cell or mouse models. These studies advanced the elucidation of molecular basis of infantile epileptic encephalopathy.

Academic Significance and Societal Importance of the Research Achievements

新規原因遺伝子とその機能変化について知見をえることにより、乳児期発症てんかん性脳症の分子病態の理解が進んだ。原因遺伝子変異が多く同定されることは、遺伝子診断できる症例が増えることを意味しており、現時点で約5割の症例で遺伝子診断が可能である。また、2遺伝子に関しては、遺伝子変異をノックインすることによるマウスモデルの確立に成功しており、更なる病態解明と治療薬の開発に繋がる研究成果である。

Research Products

• [Int'l Joint Research] University of Genoa/Istituto Italiano di Tecnologia/Meyer-University of Florence(イタリア)
• [Int'l Joint Research] Pamukkale University Hospital(トルコ)
• [Int'l Joint Research] Sheba Medical Center/Wolfson Medical Center/Schneider's Children Medical Center(イスラエル)
• [Int'l Joint Research] Kuala Lumpur Hospital(マレーシア)
• [Journal Article] Expanding the concept of peroxisomal diseases and efficient diagnostic system in Japan (2018)
  • Author(s): Takashima Shigeo、Saitsu Hirotomo、Shimozawa Nobuyuki
  • Journal Title: Journal of Human Genetics Volume: 64 Issue: 2 Pages: 145-152
  • DOI: 10.1038/s10038-018-0512-1
  • Peer Reviewed
• [Journal Article] Biallelic COLGALT1 variants are associated with cerebral small vessel disease (2018)
  • Author(s): Miyatake Satoko、Schneeberger Sacha、Koyama Norihisa、Yokochi Kenji、Ohmura Kayo、、Hennet Thierry、Matsumoto Naomichi、et al
  • Journal Title: Annals of Neurology Volume: 84 Issue: 6 Pages: 843-853
  • DOI: 10.1002/ana.25367
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] PLPBP mutations cause variable phenotypes of developmental and epileptic encephalopathy. (2018)
  • Author(s): Shiraku H#, Nakashima M#, Takeshita S# (# denotes equal contribution), Khoo CS, Haniffa M, Ch'ng GS, Takada K, Nakajima K, Ohta M, Okanishi T, Kanai S, Fujimoto A, Saitsu H, Matsumoto N*, Kato M* (*: co-correspondence).
  • Journal Title: Epilepsia Open. Volume: 3(4) Issue: 4 Pages: 495-502
  • DOI: 10.1002/epi4.12272
  • Peer Reviewed / Open Access
• [Journal Article] De novo PHACTR1 mutations in West syndrome and their pathophysiological effects (2018)
  • Author(s): Hamada Nanako、Ogaya Shunsuke、Nakashima Mitsuko、Nishijo Takuma、Sugawara Yuji、Iwamoto Ikuko、Ito Hidenori、Maki Yuki、Shirai Kentaro、Baba Shimpei、Maruyama Koichi、Saitsu Hirotomo、Kato Mitsuhiro、Matsumoto Naomichi、Momiyama Toshihiko、Nagata Koh-ichi
  • Journal Title: Brain Volume: 141 Pages: 3098-3114
  • DOI: 10.1093/brain/awy246
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GRIN2D variants in three cases of developmental and epileptic encephalopathy (2018)
  • Author(s): Tsuchida Naomi、Hamada Keisuke、Shiina Masaaki、Kato Mitsuhiro、Kobayashi Yu、Tohyama Jun、Kimura Kazue、Hoshino Kyoko、Ganesan Vigneswari、Teik Keng W.、Nakashima Mitsuko、Mitsuhashi Satomi、Mizuguchi Takeshi、Takata Atsushi、Miyake Noriko、Saitsu Hirotomo、Ogata Kazuhiro、Miyatake Satoko、Matsumoto Naomichi
  • Journal Title: Clinical Genetics Volume: 94 Issue: 6 Pages: 538-547
  • DOI: 10.1111/cge.13454
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Deletions of SCN2A and SCN3A genes in a patient with West syndrome and autistic spectrum disorder. (2018)
  • Author(s): Chong PF, Saitsu H, Sakai Y, Imagi T, Nakamura R, Matsukura M, Matsumoto N, Kira R.
  • Journal Title: Seizure. Volume: 60 Pages: 91-93
  • DOI: 10.1016/j.seizure.2018.06.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy (2018)
  • Author(s): Belal Hazrat、Nakashima Mitsuko、Matsumoto Hiroshi、Yokochi Kenji、Taniguchi-Ikeda Mariko、Aoto Kazushi、Amin Mohammed Badrul、Maruyama Azusa、Nagase Hiroaki、Mizuguchi Takeshi、Miyatake Satoko、Miyake Noriko、Iijima Kazumoto、Nonoyama Shigeaki、Matsumoto Naomichi、Saitsu Hirotomo
  • Journal Title: Human Mutation Volume: 39 Issue: 8 Pages: 1070-1075
  • DOI: 10.1002/humu.23550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] wo Japanese cases of epileptic encephalopathy associated with an FGF12 mutation. (2018)
  • Author(s): Takeguchi R#, Haginoya K# (# denotes equal contribution), Uchiyama Y, Fujita A, Nagura M, Takeshita E*, Inui T, Okubo Y, Sato R, Miyabayashi T, Togashi N, Saito T, Nakagawa E, Sugai K, Nakashima M, Saitsu H, Matsumoto N, Sasaki M.
  • Journal Title: Brain Dev. Volume: 40(8) Issue: 8 Pages: 728-732
  • DOI: 10.1016/j.braindev.2018.04.002
  • Peer Reviewed
• [Journal Article] De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy (2018)
  • Author(s): Fassio Anna、Esposito Alessandro、Kato Mitsuhiro、Saitsu Hirotomo、et al.
  • Journal Title: Brain Volume: 141 Issue: 6 Pages: 1703-1718
  • DOI: 10.1093/brain/awy092
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A case of new PCDH12 gene variants presented as dyskinetic cerebral palsy with epilepsy. (2018)
  • Author(s): Suzuki-Muromoto S# (#: correspondence), Wakusawa K, Miyabayashi T, Sato R, Okubo Y, Endo W, Inui T, Togashi N, Kato A, Oba H, Nakashima M, Saitsu H, Matsumoto N, Haginoya K.
  • Journal Title: J Hum Genet. Volume: 63(6) Issue: 6 Pages: 749-753
  • DOI: 10.1038/s10038-018-0432-0
  • Peer Reviewed
• [Journal Article] De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy (2018)
  • Author(s): Nakashima Mitsuko、Kato Mitsuhiro、Aoto Kazushi、Shiina Masaaki、Belal Hazrat、Mukaida Souichi、Kumada Satoko、Sato Atsushi、Zerem Ayelet、Lerman-Sagie Tally、Lev Dorit、Leong Huey Yin、Tsurusaki Yoshinori、Mizuguchi Takeshi、Miyatake Satoko、Miyake Noriko、Ogata Kazuhiro、Saitsu Hirotomo、Matsumoto Naomichi
  • Journal Title: Annals of Neurology Volume: 83 Issue: 4 Pages: 794-806
  • DOI: 10.1002/ana.25208
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A male case with CDKL5 -associated encephalopathy manifesting transient methylmalonic acidemia (2018)
  • Author(s): Akamine Satoshi、Ishizaki Yoshito、Sakai Yasunari、Torisu Hiroyuki、Fukai Ryoko、Miyake Noriko、Ohkubo Kazuhiro、Koga Hiroshi、Sanefuji Masafumi、Sakata Ayumi、Kimura Masahiko、Yamaguchi Seiji、Sakamoto Osamu、Hara Toshiro、Saitsu Hirotomo、Matsumoto Naomichi、Ohga Shouichi
  • Journal Title: European Journal of Medical Genetics Volume: in press Issue: 8 Pages: 451-454
  • DOI: 10.1016/j.ejmg.2018.03.003
  • Peer Reviewed
• [Journal Article] De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders (2018)
  • Author(s): Akita Tenpei、Aoto Kazushi、Kato Mitsuhiro、Shiina Masaaki、Mutoh Hiroki、Nakashima Mitsuko、Kuki Ichiro、Okazaki Shin、Magara Shinichi、Shiihara Takashi、Yokochi Kenji、Aiba Kaori、Tohyama Jun、Ohba Chihiro、Miyatake Satoko、Miyake Noriko、Ogata Kazuhiro、Fukuda Atsuo、Matsumoto Naomichi、Saitsu Hirotomo
  • Journal Title: Annals of Clinical and Translational Neurology Volume: 5 Issue: 3 Pages: 280-296
  • DOI: 10.1002/acn3.528
  • Peer Reviewed / Open Access
• [Journal Article] De novo HDAC8 mutation causes Rett-related disorder with distinctive facial features and multiple congenital anomalies (2018)
  • Author(s): Saikusa Tomoko、Hara Munetsugu、Iwama Kazuhiro、Yuge Kotaro、Ohba Chihiro、Okada Jun-ichiro、Hisano Tadashi、Yamashita Yushiro、Okamoto Nobuhiko、Saitsu Hirotomo、Matsumoto Naomichi、Matsuishi Toyojiro
  • Journal Title: Brain and Development Volume: 40 Issue: 5 Pages: 406-409
  • DOI: 10.1016/j.braindev.2017.12.013
  • Peer Reviewed / Open Access
• [Journal Article] Loss-of-function and gain-of-function mutations in PPP3CA cause two distinct disorders (2018)
  • Author(s): Mizuguchi Takeshi、Kurahashi Hirokazu、et al.
  • Journal Title: Human Molecular Genetics Volume: 27 Issue: 8 Pages: 1421-1433
  • DOI: 10.1093/hmg/ddy052
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biallelic Variants in CNPY3 , Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy (2018)
  • Author(s): Mutoh Hiroki、Kato Mitsuhiro、Akita Tenpei、Shibata Takuma、Wakamoto Hiroyuki、Ikeda Hiroko、Kitaura Hiroki、Aoto Kazushi、Nakashima Mitsuko、Wang Tianying、Ohba Chihiro、Miyatake Satoko、Miyake Noriko、Kakita Akiyoshi、Miyake Kensuke、Fukuda Atsuo、Matsumoto Naomichi、Saitsu Hirotomo
  • Journal Title: The American Journal of Human Genetics Volume: 102 Issue: 2 Pages: 321-329
  • DOI: 10.1016/j.ajhg.2018.01.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism (2018)
  • Author(s): Hiraide Takuya、Nakashima Mitsuko、Yamoto Kaori、Fukuda Tokiko、Kato Mitsuhiro、Ikeda Hiroko、Sugie Yoko、Aoto Kazushi、Kaname Tadashi、Nakabayashi Kazuhiko、Ogata Tsutomu、Matsumoto Naomichi、Saitsu Hirotomo
  • Journal Title: Human Genetics Volume: 137 Issue: 1 Pages: 95-104
  • DOI: 10.1007/s00439-017-1863-y
  • Peer Reviewed / Open Access
• [Journal Article] Detection of copy number variations in epilepsy using exome data (2018)
  • Author(s): Tsuchida N, Nakashima M, Kato M, Heyman E, Inui T, Haginoya K, Watanabe S, Chiyonobu T, Morimoto M, Ohta M, Kumakura A, Kubota M, Kumagai Y, Hamano SI, Mizuguchi T. et al.
  • Journal Title: Clinical Genetics Volume: 93 Issue: 3 Pages: 577-587
  • DOI: 10.1111/cge.13144
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Epileptic apnea in a patient with inherited glycosylphosphatidylinositol anchor deficiency and PIGT mutations. (2018)
  • Author(s): Kohashi K, Ishiyama A*, Yuasa S, Tanaka T, Miya K, Adachi Y, Sato N, Saitsu H, Ohba C, Matsumoto N, Murakami Y, Kinoshita T, Sugai K, Sasaki M.
  • Journal Title: Brain Dev Volume: 40(1) Issue: 1 Pages: 53-57
  • DOI: 10.1016/j.braindev.2017.06.005
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2 mutation (2018)
  • Author(s): Kojima K、Shirai K、Kobayashi M、Miyauchi A、Saitsu H、Matsumoto N、Osaka H、Yamagata T
  • Journal Title: Brain and Development Volume: 40 Issue: 1 Pages: 69-73
  • DOI: 10.1016/j.braindev.2017.06.004
  • Peer Reviewed
• [Journal Article] Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy (2017)
  • Author(s): Syrbe S、Harms FL、Parrini E、Montomoli M、Mutze U、Helbig KL、Polster T、Albrecht B、Bernbeck U、van Binsbergen E、Biskup S、Burglen L、Denecke J、Heron B、Heyne H O、Hoffmann GF、Hornemann F、Matsushige T、Matsuura R、Kato M、et al.
  • Journal Title: Brain Volume: 140 Issue: 9 Pages: 2322-2336
  • DOI: 10.1093/brain/awx195
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Three cases of KCNT1 mutations: malignant migrating partial seizures in infancy with massive systemic to pulmonary collateral arteries. (2017)
  • Author(s): *Kawasaki Y, Kuki I, Ehara E, Murakami Y, Okazaki S, Kawawaki H, Hara M, Watanabe Y, Kishimoto S, Suda K, Saitsu H, Matsumoto N.
  • Journal Title: J Pediatr Volume: 191 Pages: 270-274
  • DOI: 10.1016/j.jpeds.2017.08.057
  • Peer Reviewed
• [Journal Article] Equivalent missense variant in the FOXP2 and FOXP1 transcription factors causes distinct neurodevelopmental disorders. (2017)
  • Author(s): Sollis E, Deriziotis P, Saitsu H, Miyake N, Matsumoto N, Hoffer MJV, Ruivenkamp CAL, Alders M, Okamoto N, Bijlsma EK, Plomp AS, Fisher SE.
  • Journal Title: Hum Mutat Volume: 38(11) Issue: 11 Pages: 1542-1554
  • DOI: 10.1002/humu.23303
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement (2017)
  • Author(s): Hori Ikumi、Otomo Takanobu、Nakashima Mitsuko、Miya Fuyuki、et al.、Saitoh Shinji
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 3552-3552
  • DOI: 10.1038/s41598-017-02840-8
  • Peer Reviewed / Open Access
• [Journal Article] Identification of novel BCL11A variants in patients with epileptic encephalopathy: Expanding the phenotypic spectrum (2017)
  • Author(s): Yoshida M.、Nakashima M.、Okanishi T.、Kanai S.、Fujimoto A.、Itomi K.、Morimoto M.、Saitsu H.、Kato M.、Matsumoto N.、Chiyonobu T.
  • Journal Title: Clinical Genetics Volume: 93 Issue: 2 Pages: 368-373
  • DOI: 10.1111/cge.13067
  • Peer Reviewed
• [Journal Article] Novel biallelic SZT2 mutations in 3 cases of early-onset epileptic encephalopathy (2017)
  • Author(s): Tsuchida N, Nakashima M, Miyauchi A, Yoshitomi S, Kimizu T, Ganesan V, Teik KW, Ch'ng GS, Kato M, Mizuguchi T, Takata A, Miyatake S, Miyake N, Osaka H, Yamagata T, Nakajima H, Saitsu H, Matsumoto N
  • Journal Title: Clinical Genetics Volume: 93 Issue: 2 Pages: 266-274
  • DOI: 10.1111/cge.13061
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A patient with Muenke syndrome manifesting migrating neonatal seizures. (2017)
  • Author(s): Okubo Y*, Kitamura T, Anzai M, Endo W, Inui T, Takezawa Y, Suzuki-Muromoto S, Miyabayashi T, Togashi N, Oba H, Saitsu H, Matsumoto N, Haginoya K.
  • Journal Title: Brain Dev Volume: 39(10) Issue: 10 Pages: 873-876
  • DOI: 10.1016/j.braindev.2017.05.007
  • Peer Reviewed
• [Journal Article] A novel mutation in the proteolytic domain of LONP1 causes atypical CODAS syndrome. (2017)
  • Author(s): Inui T, Anzai M, Takezawa Y, Endo W, Kakisaka Y, Kikuchi A, Onuma A, Kure S, Nishino I, Ohba C, Saitsu H, Matsumoto N, Haginoya K.
  • Journal Title: J Hum Genet. Volume: - Issue: 6 Pages: 653-655
  • DOI: 10.1038/jhg.2017.11
  • NAID: 40021196214
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder (2017)
  • Author(s): Mizuguchi T, Nakashima M, Kato M, Yamada K, Okanishi T, Ekhilevitch N, Mandel H, Eran A, Toyono M, Sawaishi Y, Motoi H, Shiina M, Ogata K, Miyatake S, Miyake N, Saitsu H, Matsumoto N
  • Journal Title: Journal of Human Genetics Volume: 62 Issue: 5 Pages: 525-529
  • DOI: 10.1038/jhg.2016.163
  • NAID: 40021210259
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts. (2017)
  • Author(s): Iwama K, Mizuguchi T, Takanashi JI, Shibayama H, Shichiji M, Ito S, Oguni H, Yamamoto T, Sekine A, Nagamine S, Ikeda Y, Nishida H, Kumada S, Yoshida T, Awaya T, Tanaka R, Chikuchi R, Niwa H, Oka YI, Miyatake S, Nakashima M, Takata A, Miyake N, Ito S, Saitsu H, Matsumoto N.
  • Journal Title: Clinical Genetics Volume: - Issue: 2 Pages: 180-187
  • DOI: 10.1111/cge.12991
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rare familial TSC2 gene mutation associated with atypical phenotype presentation of Tuberous Sclerosis Complex. (2017)
  • Author(s): Fox J, Ben-Shachar S, Uliel S, Svirsky R, Saitsu H, Matsumoto N, Fattal-Valevski A.
  • Journal Title: Am J Med Genet A. Volume: 173 Issue: 3 Pages: 744-748
  • DOI: 10.1002/ajmg.a.38027
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency. (2017)
  • Author(s): Kobayashi Y, Tohyama J, Akiyama T, Magara S, Kawashima H, Akasaka N, Nakashima M, Saitsu H, Matsumoto N.
  • Journal Title: Brain Dev. Volume: 39 Issue: 3 Pages: 266-270
  • DOI: 10.1016/j.braindev.2016.09.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy. (2017)
  • Author(s): Kimizu T, Takahashi Y, Oboshi T, Horino A, Koike T, Yoshitomi S, Mori T, Yamaguchi T, Ikeda H, Okamoto N, Nakashima M, Saitsu H, Kato M, Matsumoto N, Imai K.
  • Journal Title: Brain Dev. Volume: 39 Issue: 3 Pages: 256-260
  • DOI: 10.1016/j.braindev.2016.09.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The first report of Japanese patients with asparagine synthetase deficiency (2017)
  • Author(s): Yamamoto T, Endo W, Ohnishi H, Kubota K, Kawamoto N, Inui T, Imamura A, Takanashi JI, Shiina M, Saitsu H, Ogata K, Matsumoto N, Haginoya K, Fukao T
  • Journal Title: Brain Development Volume: 39 Issue: 3 Pages: 236-242
  • DOI: 10.1016/j.braindev.2016.09.010
  • Peer Reviewed
• [Journal Article] Biallelic TBCD mutations cause early-onset neurodegenerative encephalopathy (2017)
  • Author(s): Miyake N, Fukai R, Ohba C, ... Shiina M, Ogata K, Okuno-Yuguchi J, Fueki N, Ogiso Y, Suzumura H, Watabe Y, Imataka G, Leong HY, Fattal-Valevski A, Kramer U, Miyatake S, Kato M, Okamoto N, Sato Y, Mitsuhashi S, Nishino I, Kaneko N, Nishiyama A, Tamura T, Mizuguchi T, Nakashima M, Tanaka F, Saitsu H, Matsumoto N
  • Journal Title: American Journal of Human Genetics Volume: 99 Issue: 4 Pages: 950-961
  • DOI: 10.1016/j.ajhg.2016.08.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Quinidine therapy for West syndrome with KCNTI mutation (2017)
  • Author(s): Fukuoka M, Kuki I, Kawawaki H, Okazaki S, Kim K, Hattori Y, Tsuji H, Nukui M, Inoue T, Yoshida Y, Uda T, Kimura S, Mogami Y, Suzuki Y, Okamoto N, Saitsu H, Matsumoto N.
  • Journal Title: Brain Dev. Volume: 39 Issue: 1 Pages: 80-83
  • DOI: 10.1016/j.braindev.2016.08.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] DNM1L-related encephalopathy in infancy with Leigh syndrome-like phenotype and suppression-burst. (2016)
  • Author(s): Zaha K, Matsumoto H, Itoh M, Saitsu H, Kato K, Kato M, Ogata S, Murayama K, Kishita Y, Mizuno Y, Kohda M, Nishino I, Ohtake A, Okazaki Y, Matsumoto N, Nonoyama S.
  • Journal Title: Clinical Genetics Volume: 90 Issue: 5 Pages: 472-474
  • DOI: 10.1111/cge.12805
  • Peer Reviewed
• [Journal Article] The molecular and phenotypic spectrum of IQSEC2-related epilepsy (2016)
  • Author(s): Zerem A, et al., Matsumoto N, et al.
  • Journal Title: Epilepsia Volume: 57 Issue: 11 Pages: 1858-1869
  • DOI: 10.1111/epi.13560
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association between invisible basal ganglia and ZNF335 mutations: a case report (2016)
  • Author(s): Sato R, Takanashi J, Tsuyusaki Y, Kato M, Saitsu H, Matsumoto N, Takahashi T
  • Journal Title: Pediatrics Volume: 138 Issue: 3
  • DOI: 10.1542/peds.2016-0897
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay. (2016)
  • Author(s): Saitsu H, Watanabe M, Akita T, Ohba C, Sugai K, Ong WP, Shiraishi H, Yuasa S, Matsumoto H, Beng KT, Saitoh S, Miyatake S, Nakashima M, Miyake N, Kato M, Fukuda A. and Matsumoto N.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 30072-30072
  • DOI: 10.1038/srep30072
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of SPATA5-related encephalopathy in early childhood. (2016)
  • Author(s): Kurata H, Terashima H, Nakashima M, Okazaki T, Matsumura W, Ohno K, Saito Y, Maegaki Y, Kubota M, Nanba E, Saitsu H, Matsumoto N, Kato M.
  • Journal Title: Clinical Genetics Volume: 90 Issue: 5 Pages: 437-444
  • DOI: 10.1111/cge.12813
  • Peer Reviewed
• [Journal Article] Somatic mutations in GLI3 and OFD1 involved in sonic hedgehog signaling cause hypothalamic hamartoma. (2016)
  • Author(s): Saitsu H, Sonoda M, Higashijima T, Shirozu H, Masuda H, Tohyama J, Kato M, Nakashima M, Tsurusaki Y, Mizuguchi T, Miyatake S, Miyake N, Kameyama S, Matsumoto N.
  • Journal Title: Ann Clin Transl Neurol. Volume: 24 Issue: 5 Pages: 356-65
  • DOI: 10.1002/acn3.300
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 発達期脳神経疾患の遺伝要因と分子病態の解明 (2018)
  • Author(s): 才津 浩智
  • Organizer: 第110回東海臨床遺伝・代謝懇話会
  • Invited
• [Presentation] 発達期脳神経疾患の分子病態の解明 (2018)
  • Author(s): 才津 浩智
  • Organizer: 第24回日本小児神経学会東北地方会
  • Invited
• [Presentation] 網羅的遺伝子解析による遺伝性疾患の診断 (2018)
  • Author(s): 才津 浩智
  • Organizer: 第58回日本臨床化学会年次学術集会
  • Invited
• [Presentation] 先天異常疾患と体細胞モザイク変異 (2017)
  • Author(s): 才津 浩智
  • Organizer: 第57回日本先天異常学会学術集会
  • Invited
• [Presentation] 遺伝カウンセラーが知っておくべき、網羅的遺伝子解析の実際と注意点 (2017)
  • Author(s): 才津 浩智
  • Organizer: 2017年度第一回認定遺伝カウンセラーセミナー
  • Invited
• [Presentation] Genetic Diagnosis of Epileptic Syndrome Using Next Generation Sequencing (2017)
  • Author(s): 才津 浩智
  • Organizer: The 21th Annual & Scientific Meeting of Taiwan Child Neurology Society.
  • Invited
• [Presentation] From identification of pathological variants to understanding mechanisms of epileptic syndromes: novel genes and potential mechanisms (2017)
  • Author(s): 才津 浩智
  • Organizer: The 21th Annual & Scientific Meeting of Taiwan Child Neurology Society.
  • Invited
• [Presentation] Identification of STXBP1 mutations in patients with Ohtahara syndrome (2017)
  • Author(s): 才津 浩智
  • Organizer: 14th Asian and Oceanian Congress of Child Neurology.
  • Int'l Joint Research / Invited
• [Presentation] Next-Generation Sequencing (NGS) uncovers molecules essential for human physiology. (2017)
  • Author(s): Hirotomo Saitsu
  • Organizer: 第94回生理学会大会
  • Place of Presentation: アクトシティ（浜松）
  • Invited
• [Presentation] 次世代シークエンスによる分子病態の解明 (2016)
  • Author(s): 才津浩智
  • Organizer: 第39回日本小児遺伝学会学術集会
  • Place of Presentation: 慶應義塾大学三田キャンパス（東京）
  • Invited
• [Presentation] 原因不明の小児神経疾患の遺伝子診断 (2016)
  • Author(s): 才津浩智
  • Organizer: 第46回小児神経学セミナー
  • Place of Presentation: 湘南国際村センター (神奈川)
  • Invited
• [Presentation] 脳外科疾患における体細胞モザイク変異 (2016)
  • Author(s): 才津浩智
  • Organizer: 第5回 トランスレーショナルてんかん研究会
  • Place of Presentation: 新潟グランドホテル（新潟）
  • Invited
• [Presentation] Latest Applications of Automation Systems on the Next Generation Sequencing (NGS) (2016)
  • Author(s): Hirotomo Saitsu
  • Organizer: 10th International Conference of Clinical Laboratory Automation
  • Place of Presentation: GLAD Hotel Yeouido（Seoul）
  • Int'l Joint Research / Invited
• [Book] Epilepsy 「難治性てんかんと体細胞変異」 (2018)
  • Author(s): 才津 浩智
  • Total Pages: 75
  • Publisher: メディカルレビュー社
• [Patent(Industrial Property Rights)] 重度の知的障害及び運動発達遅滞を伴う難治性てんかんの検出方法 (2016)
  • Inventor(s): 松本直通、才津浩智
  • Industrial Property Rights Holder: 公立大学法人横浜市立大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016
  • Acquisition Date: 2018