Elucidation of genetic factors and molecular pathology of neurodevelopmental disorders by a multifaceted approach

• Project/Area Number: 20H03641
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Saitsu Hirotomo 浜松医科大学, 医学部, 教授 (40402838)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2022: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2021: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2020: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: マルチオミクス解析 / インフォマティクス解析 / 尿細胞 / ゲノム編集マウス / 小児脳神経疾患 / 変異マウス / インフォマティクス / マウスモデル

Outline of Research at the Start

希少遺伝性疾患である小児脳神経疾患の分子基盤と病態の解明を目的として、下記の研究項目を推進する。
（1）最先端のインフォマティクス解析によるエクソームデータの再解析：標準化表現型情報を用いた変異の順位付けとAIでのスプライス異常予測による、エクソーム解析で見過ごされてきた病的変異の同定
（2）病的変異未同定例に対するマルチオミクス（全ゲノム＋RNA-seq）解析：エクソーム解析では同定できない、イントロンや転写調節領域の病的変異・ゲノム構造異常の同定
（3）同定された変異をゲノム編集マウスで再現：同定された変異と疾患発症の因果関係を、変異マウスを用いて実験的に証明すると同時に、その分子病態に迫る

Outline of Final Research Achievements

By reanalyzing exome data using state-of-the-art informatics analysis and by performing a multi-omics analysis combining RNA-seq and whole genome analysis using urinary cells, we succeeded in identifying causative genetic abnormalities in 50% of the cases. The analysis was particularly useful in identifying variants in intronic regions, and the prediction of splice aberrations and the evaluation of splice aberrations by RNA-seq are highly complementary to each other. The multi-omics analysis using urine cells, which can be collected noninvasively, are expected to improve the gene diagnosis rate. In addition, we reported four reports on the elucidation of molecular pathophysiology using genome-edited mice.

Academic Significance and Societal Importance of the Research Achievements

尿細胞は、皮膚線維芽細胞の代替細胞として非侵襲的に取得可能である点が優れており、今後採取方法に更なる改良を加えることで、マルチオミクス解析を用いた遺伝子解析研究におけるパラダイムシフトを起こすことが期待される。実際に尿細胞用いたRNA-seq解析で原因未同定であった3症例の原因同定に成功しており、疾患原因が不明で苦しむ患者の助けになる臨床的意義の高い研究成果である。

Research Products

• [Journal Article] Identification of pathogenic deep intronic variant and exonic LINE‐1 insertion in a patient with Meckel syndrome (2023)
  • Author(s): Miyamoto Sachiko、Nakamura Kazuyuki、Kato Mitsuhiro、Nakashima Mitsuko、Saitsu Hirotomo
  • Journal Title: Annals of Human Genetics Volume: - Issue: 4 Pages: 196-202
  • DOI: 10.1111/ahg.12507
  • Peer Reviewed
• [Journal Article] Microdeletion at ESR1 Intron 6 (DEL_6_75504) Is a Susceptibility Factor for Cryptorchidism and Hypospadias. (2023)
  • Author(s): Masunaga Y, Fujisawa Y, Massart F, Spinelli C, Kojima Y, Mizuno K, Hayashi Y, Sasagawa I, Yoshida R, Kato F, Fukami M, Kamatani N, Saitsu H, Ogata T.
  • Journal Title: J Clin Endocrinol Metab. Volume: Apr 3 Issue: 10 Pages: 1-11
  • DOI: 10.1210/clinem/dgad187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PORCN-related microphthalmia with limb anomalies: case report and literature review. (2023)
  • Author(s): Fukahori K, Yamoto K, Saitsu H, Ogata T, Nagasaki K
  • Journal Title: Am J Med Genet A Volume: 191(2) Issue: 2 Pages: 636-639
  • DOI: 10.1002/ajmg.a.63048
  • Peer Reviewed
• [Journal Article] Incomplete hippocampal inversion in patients with mutations in genes involved in sonic hedgehog signaling (2023)
  • Author(s): Higashijima Takefumi、Shirozu Hiroshi、Saitsu Hirotomo、Sonoda Masaki、Fujita Atsushi、Masuda Hiroshi、Yamamoto Tetsuya、Matsumoto Naomichi、Kameyama Shigeki
  • Journal Title: Heliyon Volume: 9 Issue: 4 Pages: e14712-e14712
  • DOI: 10.1016/j.heliyon.2023.e14712
  • Peer Reviewed
• [Journal Article] Cnpy3 mice reveal neuronal expression of Cnpy3 in the brain (2023)
  • Author(s): Islam Md. Monirul、Mutoh Hiroki、Aoto Kazushi、Belal Hazrat、Saitsu Hirotomo
  • Journal Title: Journal of Neuroscience Methods Volume: 383 Pages: 109730-109730
  • DOI: 10.1016/j.jneumeth.2022.109730
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A novel de novo KCNB1 variant altering channel characteristics in a patient with periventricular heterotopia, abnormal corpus callosum, and mild seizure outcome (2023)
  • Author(s): Hiraide Takuya、Akita Tenpei、Uematsu Kenji、Miyamoto Sachiko、Nakashima Mitsuko、Sasaki Masayuki、Fukuda Atsuo、Kato Mitsuhiro、Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: 68 Issue: 1 Pages: 25-31
  • DOI: 10.1038/s10038-022-01090-5
  • Peer Reviewed / Open Access
• [Journal Article] De novo CLCN3 variants affecting Gly327 cause severe neurodevelopmental syndrome with brain structural abnormalities (2022)
  • Author(s): Nakashima Mitsuko、Argilli Emanuela、Nakano Sayaka、Sherr Elliott H.、Kato Mitsuhiro、Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: 68 Issue: 4 Pages: 291-298
  • DOI: 10.1038/s10038-022-01106-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of KMT2A :: MATR3 fusion in a patient with acute lymphoblastic leukemia and monitoring of minimal residual disease by nanoplate digital PCR. (2022)
  • Author(s): Komatsu K, Sakaguchi K, Shimizu D, Yamoto K, Kato F, Ogata T, Saitsu H
  • Journal Title: Pediatr Blood Cancer Volume: e30120 Issue: 4
  • DOI: 10.1002/pbc.30120
  • Peer Reviewed
• [Journal Article] Cognitive Impairment in a Complex Family With AAGGG and ACAGG Repeat Expansions in RFC1 Detected by ExpansionHunter Denovo (2022)
  • Author(s): Watanabe Kazuki、Nakashima Mitsuko、Wakatsuki Rie、Bunai Tomoyasu、Ouchi Yasuomi、Nakamura Tomohiko、Miyajima Hiroaki、Saitsu Hirotomo
  • Journal Title: Neurology Genetics Volume: 8 Issue: 3
  • DOI: 10.1212/nxg.0000000000000682
  • Peer Reviewed / Open Access
• [Journal Article] Generation of Flag/DYKDDDDK Epitope Tag Knock-In Mice Using i-GONAD Enables Detection of Endogenous CaMKIIα and β Proteins (2022)
  • Author(s): Aoto Kazushi、Takabayashi Shuji、Mutoh Hiroki、Saitsu Hirotomo
  • Journal Title: International Journal of Molecular Sciences Volume: 23 Issue: 19 Pages: 11915-11915
  • DOI: 10.3390/ijms231911915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and molecular findings in three Japanese patients with N-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG) (2022)
  • Author(s): Yohei Masunaga, Gen Nishimura, Koji Takahashi, Tomiyuki Hishiyama, Masatoshi Imamura, Kenichi Kashimada, Machiko Kadoya, Yoshinao Wada, Nobuhiko Okamoto, Daiju Oba, Hirofumi Ohashi, Mitsuru Ikeno, Yuko Sakamoto, Maki Fukami, Hirotomo Saitsu, Tsutomu Ogata
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 17079-17079
  • DOI: 10.1038/s41598-022-21751-x
  • Peer Reviewed / Open Access
• [Journal Article] Familial Pseudohypoparathyroidism Type IB Associated with an SVA Retrotransposon Insertion in the GNAS Locus (2022)
  • Author(s): Sayaka Kawashima, Akiko Yuno, Shinichiro Sano, Masayo Kagami
  • Journal Title: J Bone Miner Res . Volume: 10 Issue: 10 Pages: 1850-1859
  • DOI: 10.1002/jbmr.4652
  • Peer Reviewed / Open Access
• [Journal Article] A TUBB4A Met363Thr variant in pediatric hypomyelination without atrophy of the basal ganglia (2022)
  • Author(s): Hashiguchi Marina、Monden Yukifumi、Nozaki Yasuyuki、Watanabe Kazuki、Nakashima Mitsuko、Saitsu Hirotomo、Yamagata Takanori、Osaka Hitoshi
  • Journal Title: Human Genome Variation Volume: 9 Issue: 1 Pages: 19-19
  • DOI: 10.1038/s41439-022-00198-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A New Case With Cortical Malformation Caused by Biallelic Variants in <i>LAMC3</i> (2022)
  • Author(s): Abe Kazuo、Ando Kumiko、Kato Mitsuhiro、Saitsu Hirotomo、Nakashima Mitsuko、Aoki Shintaro、Kimura Takashi
  • Journal Title: Neurology Genetics Volume: 8 Issue: 3
  • DOI: 10.1212/nxg.0000000000000680
  • Peer Reviewed / Open Access
• [Journal Article] A new case of concurrent existence of PRRT2-associated paroxysmal movement disorders with c.649dup variant and 16p11.2 microdeletion syndrome (2022)
  • Author(s): Komatsu Kazuyuki、Fukumura Shinobu、Minagawa Kimio、Nakashima Mitsuko、Saitsu Hirotomo
  • Journal Title: Brain and Development Volume: 44 Issue: 7 Pages: 474-479
  • DOI: 10.1016/j.braindev.2022.03.008
  • Peer Reviewed
• [Journal Article] ACAN biallelic variants in a girl with severe idiopathic short stature (2022)
  • Author(s): Masunaga Y, Ohkubo Y, Nishimura G, Ueno T, Fujisawa Y, Fukami M, Saitsu H, Ogata T
  • Journal Title: J Hum Genet Volume: - Issue: 8 Pages: 481-486
  • DOI: 10.1038/s10038-022-01030-3
  • Peer Reviewed
• [Journal Article] Retinitis pigmentosa with optic neuropathy and COQ2 mutations: A case report (2022)
  • Author(s): Kurata K, Hosono K, Takayama M, Tatsuno M, Saitsu H, Ogata T, Hotta Y
  • Journal Title: Am J Ophthalmol Case Rep Volume: - Pages: 101298-101298
  • DOI: 10.1016/j.ajoc.2022.101298
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neurochemistry evaluated by MR spectroscopy in a patient with SPTAN1-related developmental and epileptic encephalopathy (2022)
  • Author(s): Sakata Yuka、Sano Kentaro、Aoki Shintaro、Saitsu Hirotomo、Takanashi Jun-ichi
  • Journal Title: Brain and Development Volume: - Issue: 6 Pages: 415-420
  • DOI: 10.1016/j.braindev.2022.02.001
  • Peer Reviewed
• [Journal Article] Two novel heterozygous variants in ATP1A3 cause movement disorders (2022)
  • Author(s): Furukawa Shogo、Miyamoto Sachiko、Fukumura Shinobu、Kubota Kazuo、Taga Toshiaki、Nakashima Mitsuko、Saitsu Hirotomo
  • Journal Title: Human Genome Variation Volume: 9 Issue: 1
  • DOI: 10.1038/s41439-022-00184-y
  • Peer Reviewed / Open Access
• [Journal Article] Maternal Uniparental Isodisomy of Chromosome 4 and 8 in Patients with Retinal Dystrophy: SRD5A3-Congenital Disorders of Glycosylation and RP1-Related Retinitis Pigmentosa (2022)
  • Author(s): Tachibana Nobutaka、Hosono Katsuhiro、Nomura Shuhei、Arai Shinji、Torii Kaoruko、Kurata Kentaro、Sato Miho、Shimakawa Shuichi、Azuma Noriyuki、Ogata Tsutomu、Wada Yoshinao、Okamoto Nobuhiko、Saitsu Hirotomo、Nishina Sachiko、Hotta Yoshihiro
  • Journal Title: Genes Volume: 13 Issue: 2 Pages: 359-359
  • DOI: 10.3390/genes13020359
  • Peer Reviewed / Open Access
• [Journal Article] An intronic GNAO1 variant leading to in-frame insertion cause movement disorder controlled by deep brain stimulation (2022)
  • Author(s): Miyamoto Sachiko、Nakashima Mitsuko、Fukumura Shinobu、Kumada Satoko、Saitsu Hirotomo
  • Journal Title: neurogenetics Volume: 23 Issue: 2 Pages: 129-135
  • DOI: 10.1007/s10048-022-00686-5
  • Peer Reviewed
• [Journal Article] Compound heterozygous ADAMTS9 variants in Joubert syndrome-related disorders without renal manifestation (2022)
  • Author(s): Matsushita Hiroko Baber、Hiraide Takuya、Hayakawa Katsumi、Okano Sozo、Nakashima Mitsuko、Saitsu Hirotomo、Kato Mitsuhiro
  • Journal Title: Brain and Development Volume: 44 Issue: 2 Pages: 161-165
  • DOI: 10.1016/j.braindev.2021.10.004
  • Peer Reviewed
• [Journal Article] Genome sequencing and RNA sequencing of urinary cells reveal an intronic FBN1 variant causing aberrant splicing (2022)
  • Author(s): Hiraide Takuya、Shimizu Kenji、Miyamoto Sachiko、Aoto Kazushi、Nakashima Mitsuko、Yamaguchi Tomomi、Kosho Tomoki、Ogata Tsutomu、Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: - Issue: 7 Pages: 387-392
  • DOI: 10.1038/s10038-022-01016-1
  • Peer Reviewed
• [Journal Article] Elucidation of pathological mechanism caused by human disease mutation in CaMKIIβ (2022)
  • Author(s): Mutoh H, Aoto K, Miyazaki T, Fukuda A, Saitsu H.
  • Journal Title: Journal of Neuroscience Research Volume: 100 Issue: 3 Pages: 880-896
  • DOI: 10.1002/jnr.25013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A novel intronic PORCN variant creating an alternative splice acceptor site in a mother and her daughter with focal dermal hypoplasia (2022)
  • Author(s): Yamoto K, Okada S, Kato F, Fujisawa Y, Fukami M, Saitsu H, Ogata T
  • Journal Title: Am J Med Genet A Volume: - Issue: 5 Pages: 1612-1617
  • DOI: 10.1002/ajmg.a.62649
  • Peer Reviewed
• [Journal Article] Retrotransposition disrupting EBP in a girl and her mother with X-linked dominant chondrodysplasia punctata (2022)
  • Author(s): Hiraide T, Masunaga Y, Honda A, Kato F, Fukuda T, Fukami M, Nakashima M, Saitsu H, Ogata T
  • Journal Title: J Hum Genet Volume: - Issue: 5 Pages: 303-306
  • DOI: 10.1038/s10038-021-01000-1
  • Peer Reviewed
• [Journal Article] SCN8A-related developmental and epileptic encephalopathy with ictal asystole requiring cardiac pacemaker implantation (2021)
  • Author(s): Negishi Yutaka、Aoki Yusuke、Itomi Kazuya、Yasuda Kazushi、Taniguchi Hiroaki、Ishida Atsushi、Arakawa Takeshi、Miyamoto Sachiko、Nakashima Mitsuko、Saitsu Hirotomo、Saitoh Shinji
  • Journal Title: Brain and Development Volume: 43 Issue: 7 Pages: 804-808
  • DOI: 10.1016/j.braindev.2021.03.004
  • Peer Reviewed
• [Journal Article] Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review (2021)
  • Author(s): Watanabe Kazuki、Nakashima Mitsuko、Kumada Satoko、Mashimo Hideaki、Enokizono Mikako、Yamada Keitaro、Kato Mitsuhiro、Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: 66 Issue: 12 Pages: 1193-1197
  • DOI: 10.1038/s10038-021-00956-4
  • Peer Reviewed
• [Journal Article] Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing (2021)
  • Author(s): Hiraide T, Yamoto K, Masunaga Y, Asahina M, Endoh Y, Ohkubo Y, Matsubayashi T, Tsurui S, Yamada H, Yanagi K, Nakashima M, Hirano K, Sugimura H, Fukuda T, Ogata T, Saistu T
  • Journal Title: Clin Genet Volume: 100 Issue: 1 Pages: 40-50
  • DOI: 10.1111/cge.13951
  • Peer Reviewed
• [Journal Article] A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies (2021)
  • Author(s): Miyamoto Sachiko、Kato Mitsuhiro、Sugiyama Kenji、Horiguchi Ryo、Nakashima Mitsuko、Aoto Kazushi、Mutoh Hiroki、Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: 66 Issue: 12 Pages: 1189-1192
  • DOI: 10.1038/s10038-021-00953-7
  • Peer Reviewed
• [Journal Article] Global developmental delay, systemic dysmorphism and epilepsy in a patient with a de novo U2AF2 variant. (2021)
  • Author(s): Hiraide T, Tanaka T, Masunaga Y, Ohkubo Y, Nakashima M, Fukuda T, Ogata T, Saitsu H
  • Journal Title: J Hum Genet Volume: - Issue: 12 Pages: 1185-1187
  • DOI: 10.1038/s10038-021-00948-4
  • Peer Reviewed
• [Journal Article] Novel ALG12 variants and hydronephrosis in siblings with impaired N-glycosylation (2021)
  • Author(s): Hiraide Takuya、Wada Yoshinao、Matsubayashi Tomoko、Kadoya Machiko、Masunaga Yohei、Ohkubo Yumiko、Nakashima Mitsuko、Okamoto Nobuhiko、Ogata Tsutomu、Saitsu Hirotomo
  • Journal Title: Brain and Development Volume: 43 Issue: 9 Pages: 945-951
  • DOI: 10.1016/j.braindev.2021.05.013
  • Peer Reviewed
• [Journal Article] Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies (2021)
  • Author(s): Miyamoto Sachiko、Kato Mitsuhiro、et al and Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: 66 Issue: 11 Pages: 1061-1068
  • DOI: 10.1038/s10038-021-00932-y
  • NAID: 120007167202
  • Peer Reviewed
• [Journal Article] ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H(+)-ATPases is essential for brain development in humans and mice (2021)
  • Author(s): Aoto K, Kato M, Akita T, Nakashima M, Mutoh H, Akasaka N, Tohyama J, Nomura Y, Hoshino K, Ago Y, Tanaka R, Epstein O, Ben-Haim R, Heyman E, Miyazaki T, Belal H, Takabayashi S, Ohba C, Takata A, Mizuguchi T, Miyatake S, Miyake N, Fukuda A, Matsumoto N and Saitsu H
  • Journal Title: Nat Commun Volume: 12 Issue: 1 Pages: 2107-2107
  • DOI: 10.1038/s41467-021-22389-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ZNF445: a homozygous truncating variant in a patient with Temple syndrome and multilocus imprinting disturbance (2021)
  • Author(s): Kagami M, Hara-Isono K, Matsubara K, Nakabayashi K, Narumi S, Fukami M, Ohkubo Y, Saitsu H, Takada S, Ogata T
  • Journal Title: Clin Epigenetics Volume: 13 Issue: 1 Pages: 119-119
  • DOI: 10.1186/s13148-021-01106-5
  • Peer Reviewed / Open Access
• [Journal Article] Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy, dysmorphic features, and hepatic dysfunction (2021)
  • Author(s): Anzai Rie、Tsuji Megumi、Yamashita Sumimasa、Wada Yoshinao、Okamoto Nobuhiko、Saitsu Hirotomo、Matsumoto Naomichi、Goto Tomohide
  • Journal Title: Brain and Development Volume: 43 Issue: 3 Pages: 402-410
  • DOI: 10.1016/j.braindev.2020.10.013
  • Peer Reviewed
• [Journal Article] Familial periodic paralysis associated with a rare KCNJ5 variant that supposed to have incomplete penetrance (2021)
  • Author(s): Hiraide Takuya、Fukumura Shinobu、Yamamoto Akiyo、Nakashima Mitsuko、Saitsu Hirotomo
  • Journal Title: Brain and Development Volume: 43 Issue: 3 Pages: 470-474
  • DOI: 10.1016/j.braindev.2020.10.010
  • Peer Reviewed
• [Journal Article] De novo variants in CELF2 that disrupt the nuclear localization signal cause developmental and epileptic encephalopathy (2021)
  • Author(s): Itai T, Hamanaka K, Sasaki K, Saitsu H, Miyatake S, Matsumoto N et al.
  • Journal Title: Hum Mutat Volume: 42 Issue: 1 Pages: 66-76
  • DOI: 10.1002/humu.24130
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phenotypic overlap between pyruvate dehydrogenase complex deficiency and FOXG1 syndrome (2021)
  • Author(s): Akaba Yuichi、Takahashi Satoru、Takeguchi Ryo、Tanaka Ryosuke、Nabatame Shin、Saitsu Hirotomo、Matsumoto Naomichi
  • Journal Title: Clinical Case Reports Volume: 9 Issue: 3 Pages: 1711-1715
  • DOI: 10.1002/ccr3.3883
  • Peer Reviewed
• [Journal Article] De novo ATP1A3 variants cause polymicrogyria (2021)
  • Author(s): Miyatake Satoko、Kato Mitsuhiro、Kumamoto Takuma、Hirose Tomonori、他
  • Journal Title: Science Advances Volume: 7 Issue: 13 Pages: 2368-2368
  • DOI: 10.1126/sciadv.abd2368
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of early-onset epileptic encephalopathy with involuntary movements - Case series and literature review. (2021)
  • Author(s): Arisaka A, Nakashima M, Kumada S, Inoue K, Nishida H, Mashimo H, Kashii H, Kato M, Maruyama K, Okumura A, Saitsu H, Matsumoto N, Fukuda M.
  • Journal Title: Epilepsy Behav Rep. Volume: 15 Pages: 100417-100417
  • DOI: 10.1016/j.ebr.2020.100417
  • Peer Reviewed / Open Access
• [Journal Article] A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features (2020)
  • Author(s): Fukuda Tokiko、Hiraide Takuya、Yamoto Kaori、Nakashima Mitsuko、Kawai Tomoko、Yanagi Kumiko、Ogata Tsutomu、Saitsu Hirotomo
  • Journal Title: European Journal of Medical Genetics Volume: 63 Issue: 4 Pages: 103804-103804
  • DOI: 10.1016/j.ejmg.2019.103804
  • Peer Reviewed
• [Journal Article] POLR3A variants in striatal involvement without diffuse hypomyelination (2020)
  • Author(s): Hiraide Takuya、Kubota Kazuo、Kono Yu、Watanabe Seiji、Matsubayashi Tomoko、Nakashima Mitsuko、Kaname Tadashi、Fukao Toshiyuki、Shimozawa Nobuyuki、Ogata Tsutomu、Saitsu Hirotomo
  • Journal Title: Brain and Development Volume: 42 Issue: 4 Pages: 363-368
  • DOI: 10.1016/j.braindev.2019.12.012
  • NAID: 120007038334
  • Peer Reviewed
• [Journal Article] Fulminant myocarditis following recurrent generalized erythrokeratoderma in a child with a heterozygous GJA1 variant (2020)
  • Author(s): Kobayashi Hironobu、Shiohama Tadashi、Nakashima Mitsuko、Saitsu Hirotomo、Suga Yasushi、Ebata Ryota、Shimojo Naoki
  • Journal Title: American Journal of Medical Genetics Part A Volume: 182 Issue: 8 Pages: 1933-1938
  • DOI: 10.1002/ajmg.a.61626
  • Peer Reviewed
• [Journal Article] De Novo Truncating Variants in the Last Exon of SEMA6B Cause Progressive Myoclonic Epilepsy (2020)
  • Author(s): Hamanaka Kohei、Imagawa Eri、Koshimizu Eriko、Miyatake Satoko、Tohyama Jun、Yamagata Takanori、Miyauchi Akihiko、Ekhilevitch Nina、Nakamura Fumio、Kawashima Takeshi、Takata Atsushi、Miyake Noriko、Matsumoto Naomichi et al.,
  • Journal Title: The American Journal of Human Genetics Volume: 106(4) Issue: 4 Pages: 549-558
  • DOI: 10.1016/j.ajhg.2020.02.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] De novo variants in CUL3 are associated with global developmental delays with or without infantile spasms (2020)
  • Author(s): Nakashima Mitsuko、Kato Mitsuhiro、Matsukura Masaru、Kira Ryutaro、Ngu Lock-Hock、Lichtenbelt Klaske D.、van Gassen Koen L. I.、Mitsuhashi Satomi、Saitsu Hirotomo、Matsumoto Naomichi
  • Journal Title: Journal of Human Genetics Volume: 65 Issue: 9 Pages: 727-734
  • DOI: 10.1038/s10038-020-0758-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Long-term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1 (2020)
  • Author(s): Hayashi Takaaki、Hosono Katsuhiro、Kubo Akiko、Kurata Kentaro、Katagiri Satoshi、Mizobuchi Kei、Kurai Minehiro、Mamiya Norihito、Kondo Mineo、Tachibana Toshiaki、Saitsu Hirotomo、Ogata Tsutomu、Nakano Tadashi、Hotta Yoshihiro
  • Journal Title: American Journal of Medical Genetics Part A Volume: 印刷中 Issue: 6 Pages: 1500-1505
  • DOI: 10.1002/ajmg.a.61575
  • Peer Reviewed
• [Journal Article] De novo CACNA1G variants in developmental delay and early-onset epileptic encephalopathies (2020)
  • Author(s): Misako Kunii, Hiroshi Doi, Shunta Hashiguchi, Toyojiro Matsuishi, Yasunari Sakai, Mizue Iai, Masaki Okubo, Haruko Nakamura, Keita Takahashi, Atsuko Katsumoto, Mikiko Tada, Hideyuki Takeuchi, Taro Ishikawa, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto, Fumiaki Tanaka
  • Journal Title: Journal of the Neurological Sciences Volume: 416 Pages: 117047-117047
  • DOI: 10.1016/j.jns.2020.117047
  • Peer Reviewed / Open Access
• [Journal Article] Prenatal clinical manifestations in individuals with COL4A1/2 variants (2020)
  • Author(s): Itai T, Miyatake S, Taguri M, Nakashima M, Saitsu H, Matsumoto N et al.
  • Journal Title: J Med Genet Volume: 0 Issue: 8 Pages: 106896-106896
  • DOI: 10.1136/jmedgenet-2020-106896
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical and genetic characteristics of patients with Doose syndrome (2020)
  • Author(s): Hinokuma N, Nakashima M, Asai H, Nakamura K, Itai T, Miyatake S, Saitsu H, Matsumoto N, Kato M et al.
  • Journal Title: Epilepsia Open Volume: 5 Issue: 3 Pages: 442-450
  • DOI: 10.1002/epi4.12417
  • Peer Reviewed / Open Access
• [Journal Article] GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons. (2020)
  • Author(s): Akamine S, Okuzono S, Yamamoto H, Setoyama D, Sagata N, Ohgidani M, Kato TA, Ishitani T, Kato H, Masuda K, Matsushita Y, Ono H, Ishizaki Y, Sanefuji M, Saitsu H, Matsumoto N, Kang D, Kanba S, Nakabeppu Y, Sakai Y, Ohga S.
  • Journal Title: FASEB J Volume: 34 Issue: 12 Pages: 16601-16621
  • DOI: 10.1096/fj.202001113r
  • Peer Reviewed / Open Access
• [Journal Article] Novel EXOSC9 variants cause pontocerebellar hypoplasia type 1D with spinal motor neuronopathy and cerebellar atrophy (2020)
  • Author(s): Sakamoto Masamune、Iwama Kazuhiro、Sekiguchi Futoshi、Mashimo Hideaki、Kumada Satoko、Ishigaki Keiko、Okamoto Nobuhiko、Behnam Mahdiyeh、Ghadami Mohsen、Koshimizu Eriko、Miyatake Satoko、Mitsuhashi Satomi、Mizuguchi Takeshi、Takata Atsushi、Saitsu Hirotomo、Miyake Noriko、Matsumoto Naomichi
  • Journal Title: Journal of Human Genetics Volume: 66 Issue: 4 Pages: 401-407
  • DOI: 10.1038/s10038-020-00853-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Myoclonic tremor status as a presenting symptom of adenylosuccinate lyase deficiency (2020)
  • Author(s): Andelman-Gur Michal M.、Saitsu Hirotomo、Matsumoto Naomichi、Spiegel Ronen、Yosovich Keren、Lev Dorit、Lerman-Sagie Tally、Blumkin Lubov
  • Journal Title: European Journal of Medical Genetics Volume: 63 Issue: 12 Pages: 104061-104061
  • DOI: 10.1016/j.ejmg.2020.104061
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A de novo GABRB2 variant associated with myoclonic status epilepticus and rhythmic high-amplitude delta with superimposed (poly) spikes (RHADS) (2020)
  • Author(s): Nishikawa Aiko、Otani Yui、Ito Susumu、Nagata Satoru、Shiota Mutsuki、Takanashi Jun-ichi、Nakashima Mitsuko、Saitsu Hirotomo、Matsumoto Naomichi、Oguni Hirokazu
  • Journal Title: Epileptic Disorders Volume: 22 Issue: 4 Pages: 476-481
  • DOI: 10.1684/epd.2020.1183
  • Peer Reviewed
• [Journal Article] A recurrent TMEM106B mutation in hypomyelinating leukodystrophy: A rapid diagnostic assay (2020)
  • Author(s): Ikemoto Satoru、Hamano Shin-ichiro、Kikuchi Kenjiro、Koichihara Reiko、Hirata Yuko、Matsuura Ryuki、Hiraide Takuya、Nakashima Mitsuko、Inoue Ken、Kurosawa Kenji、Saitsu Hirotomo
  • Journal Title: Brain and Development Volume: 42 Issue: 8 Pages: 603-606
  • DOI: 10.1016/j.braindev.2020.06.002
  • Peer Reviewed
• [Journal Article] Identification of a deep intronic POLR3A variant causing inclusion of a pseudoexon derived from an Alu element in Pol III-related leukodystrophy (2020)
  • Author(s): Hiraide Takuya、Nakashima Mitsuko、Ikeda Takahiro、Tanaka Daisuke、Osaka Hitoshi、Saitsu Hirotomo
  • Journal Title: Journal of Human Genetics Volume: 65 Issue: 10 Pages: 921-925
  • DOI: 10.1038/s10038-020-0786-y
  • NAID: 120007143500
  • Peer Reviewed
• [Journal Article] POLR1C variants dysregulate splicing and cause hypomyelinating leukodystrophy (2020)
  • Author(s): Kashiki Hitoshi、Li Heng、Miyamoto Sachiko、Ueno Hiroe、Tsurusaki Yoshinori、Ikeda Chizuru、Kurata Hirofumi、Okada Takumi、Shimazu Tomoyuki、Imamura Hoseki、Enomoto Yumi、Takanashi Jun-ichi、Kurosawa Kenji、Saitsu Hirotomo、Inoue Ken
  • Journal Title: Neurology Genetics Volume: 6 Issue: 6 Pages: 1-7
  • DOI: 10.1212/nxg.0000000000000524
  • Peer Reviewed / Open Access
• [Presentation] 希少疾患の診断の進歩: WES再解析/WGS/RNA-seq解析の現状と有用性 (2022)
  • Author(s): 才津浩智
  • Organizer: 日本人類遺伝学会第67回大会
• [Presentation] 全ゲノムおよびトランスクリプトーム解析による疾患原因の同定 (2022)
  • Author(s): 才津浩智
  • Organizer: 第62回日本先天異常学会学術集会
• [Presentation] 網羅的遺伝子解析による病的意義不明例の検出と病態・機能解析 (2022)
  • Author(s): 才津浩智
  • Organizer: 第64回日本小児神経学会学術集会
• [Presentation] ATP6V0A1 encoding the α1-subunit of the V0 domain of vacuolar H+-ATPases is essential for brain development in humans and mice (2021)
  • Author(s): Hirotomo Saitsu et al.
  • Organizer: 日本人類遺伝学会第66回大会 第28回日本遺伝子診療学会大会 合同開
• [Presentation] シンポジウム「ゲノム異常と先天異常」 (2020)
  • Author(s): 才津浩智
  • Organizer: 第29回日本形成外科学会基礎学術集会
  • Invited
• [Presentation] 教育講演「小児神経疾患の遺伝学的原因検索から病態解明へ」 (2020)
  • Author(s): 才津浩智
  • Organizer: 第62回日本小児神経学会学術集会
  • Invited