Identification of the genes associated with spina bifida harboring intellectual disability

• Project/Area Number: 26462225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Wakamatsu Nobuaki 愛知県心身障害者コロニー発達障害研究所, 遺伝学部, 部長 (60274198)
• Research Collaborator: NOMURA NORIKO ; FUKUSHI DAISUKE ; KUROSAWA KENJI ; YOKOCHI KENJI
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 二分脊椎 / 2番染色体短腕 / 部分トリソミー / 5p-症候群 / 知的障害 / アレイCGH / トリソミー

Outline of Final Research Achievements

The partial trisomy 2p24 has been reported to be associated with NTDs such as anencephaly, encephalocele, and spina bifida. We report the cases of 2 siblings with trisomy 2p24.3pter and monosomy 5p14.3pter caused by paternal translocation t(2;5)(p24.3;p14.3). Of the 2 siblings, the elder sister had spina bifida. We determined the nucleotide sequences of chromosomal breakpoints and found that the sizes of trisomy 2p and monosomy 5p segments were 18.77 and 17.89 Mb, respectively. NTDs were present in 4 of 7 previously reported patients as well as in 1 patient examined of the present study. Comparison of clinical features of the patients with trisomy 2p and monosomy 5p including our cases, we identified characteristic features of trisomy 2p24.3pter. Increased gene dosages of dosage sensitive genes or genes at the trisomy segment (2p24.3) of the presented patients could be associated with NTDs of patients with trisomy 2p.

Research Products

• [Journal Article] The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS). (2017)
  • Author(s): Suzuki Y, Enokido Y, Yamada K, Inaba M, Kuwata K, Hanada N, Morishita T, Mizuno S, Wakamatsu N
  • Journal Title: Oncotarget in press Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular reminiscent of Mowat-Wilson syndrome with Ehlers-Danlos syndrome. (2017)
  • Author(s): Teraishi M, Takaishi M, Nakajima K, Ikeda M, Higashi Y, Shimoda S, Asada Y, Hijikata A, Ohara O, Hirai Y, Mizuno S, Fukada T, Furukawa T, Wakamatsu N, Sano S.
  • Journal Title: Scientific Report Volume: 7:46565 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep46565
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] phenotypes from infantile lethality to mild learning difficulties (2017)
  • Author(s): Tanigawa J, Mimatsu H, Mizuno S, Okamoto N, Fukushi D, Tominaga K, Kidokoro H, Muramatsu Y, Nishi E, Nakamura S, Motooka D, Nomura N, Hayasaka K, Niihori T, Aoki Y, Nabatame S, Hayakawa M, Natsume J, Ozono K, Kinoshita T, Wakamatsu N, Murakami Y
  • Journal Title: Human Mutation Volume: 印刷中 Issue: 7 Pages: 805-815
  • DOI: 10.1002/humu.23219
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel mutation in HPRT1 causing a splicing error with multiple variations. (2017)
  • Author(s): Baba S, Saito T, Yamada Y, Takeshita E, Nomura N, Yamada K, Wakamatsu N, Sasaki M.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids Volume: 36 Issue: 1 Pages: 1-6
  • DOI: 10.1080/15257770.2016.1163381
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hearing impairment in a female infant with interstitial deletion of 2q24.1q24.3. (2016)
  • Author(s): Ono H, Kurosawa K, Wakamatsu N, Masuda S.
  • Journal Title: Congenit Anom (Kyoto) Epub ahead of print Volume: 印刷中 Issue: 4 Pages: 118-121
  • DOI: 10.1111/cga.12207
  • NAID: 130008142364
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion (2015)
  • Author(s): Yamada K, Aiba K, Kitaura Y, Kondo Y, Nomura N, Nakamura Y, Fukushi D, Murayama K, Shimomura Y, Pitt J, Yamaguchi S, Yokochi K, Wakamatsu N
  • Journal Title: Journal of Medical Genetics Volume: 52 Issue: 10 Pages: 691-698
  • DOI: 10.1136/jmedgenet-2015-103231
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] De novo inbred heterozygous Zeb2/Sip1 mutant mice uniquely generated by germ-line conditional knockout exhibit craniofacial, callosal and behavioral defects associated with Mowat-Wilson syndrome (2015)
  • Author(s): 51.Takagi T, Nishizaki Y, Matsui F, Wakamatsu N, Higashi Y.
  • Journal Title: Hum Mol Genet. Volume: 24 Issue: 22 Pages: 6390-6402
  • DOI: 10.1093/hmg/ddv350
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 分子遺伝学的検査にて本邦初の変異と家族内発症が明らかになったLesch-Nyhan variantの一家系． (2015)
  • Author(s): 松田安史，山田裕一，若松延昭，三澤美和，江川克哉，山内高弘，中村真希子，長谷川弘，市田公美，上田孝典
  • Journal Title: 痛風と核酸代謝 Volume: 39 Pages: 121-128
  • NAID: 130005114182
  • Peer Reviewed
• [Journal Article] Mutations in HADHB, which encodes the β-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy. (2014)
  • Author(s): Naiki M, Ochi N, Kato YS , Purevsuren J, Yamada K, Kimura R, Fukushi D, Hara S, Yamada Y, Kumagai T, Yamaguchi S, Wakamatsu N
  • Journal Title: Am J Med Genet A Volume: in press Issue: 5 Pages: 1180-1187
  • DOI: 10.1002/ajmg.a.36434
  • Peer Reviewed
• [Journal Article] The spectrum of ZEB2 mutations causing the Mowat-Wilson syndrome in Japanese populations. (2014)
  • Author(s): Yamada Y, Nomura N, Yamada K, et al. （32名中3番目）
  • Journal Title: Am J Med Genet A Volume: in press Issue: 8 Pages: 1899-908
  • DOI: 10.1002/ajmg.a.36551
  • Peer Reviewed
• [Journal Article] Hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiencies: HPRT1 mutations in new Japanese families and PRPP concentration. (2014)
  • Author(s): Yamada Y, Nomura N, Yamada K, et al.
  • Journal Title: Nucleosides Nucleotides Nucleic Acids Volume: 33 Issue: 4-6 Pages: 218-222
  • DOI: 10.1080/15257770.2013.865743
  • Peer Reviewed
• [Journal Article] Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2. (2014)
  • Author(s): Fukushi D, Yamada K, Nomura N, Naiki M, Kimura R, Yamada Y, Kumagai T, Yamaguchi K, Miyake Y, Wakamatsu N
  • Journal Title: Am J Med Genet A Volume: 164(4) Issue: 4 Pages: 924-933
  • DOI: 10.1002/ajmg.a.36373
  • Peer Reviewed
• [Journal Article] Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis. (2014)
  • Author(s): Yamada K, Naiki M, Hoshino S, et al.
  • Journal Title: Mol Genet Metab Rep Volume: 1 Pages: 455-460
  • Peer Reviewed / Open Access
• [Presentation] ヒトECHS1の生化学的解析と軽症型ECHS1欠損症の病態解明 (2015)
  • Author(s): 山田憲一郎, 相場佳織, 北浦靖之, 近藤雄介, 野村紀子, 中村勇治, 福士大輔, 村山圭, 下村吉治, James Pitt, 山口清次, 横地健治, 若松延昭
  • Organizer: BMB2015・第88回日本生化学会大会・第38回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-04
• [Presentation] PIK3CA-related overgrowth spectrum (PROS)の病態解明 (2015)
  • Author(s): 鈴木康予, 榎戸 靖, 山田憲一郎, 花田直樹, 森下 剛, 水野誠司, 若松延昭
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-03
• [Presentation] 軽症Short-chain enoyl-CoA hydratase (ECHS1)欠損症の生化学的解析：診断に有効な化合物の同定 (2015)
  • Author(s): 若松延昭, 山田憲一郎, 北浦靖之, 近藤雄介, 野村紀子, 村山圭, 山口清次, 下村吉治, 横地健治, James Pitt
  • Organizer: 第57回日本先天代謝異常学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2015-11-12
• [Presentation] Biotin-Responsive Basal Ganglia Disease(BBGD)と診断した幼児例 (2015)
  • Author(s): 榊原崇文, 高木久美子, 越智聡史, 竹下佳弘, 山田憲一郎, 若松延昭, 嶋緑倫
  • Organizer: 第58回日本小児神経学会近畿地方会
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-24
• [Presentation] SF3B4の欠失が見られるNager症候群の1症例 (2015)
  • Author(s): 福士大輔, 水野誠司, 稲葉美枝, 鈴木 香, 野村紀子, 鈴木康予, 山田憲一郎, 若松延昭
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-16
• [Presentation] Leigh disease and the valine pathway. (2015)
  • Author(s): Pitt J, Peters H, Yaplito-Lee J, Boneh A, Ferdinandusse S, Ruiter J, Wanders RJA, Kok F, Boy R, Korman SH, Fitzsimons PE, Crushell E, Hughes J, Yamaguchi S, Goto Y, Wakamatsu N, Yamada K, Yokochi K, Chen BC, Ngu LH
  • Organizer: Annual Symposium 2015, Society for the Study of Inborn Errors of Metabolism
  • Place of Presentation: Lyon, France
  • Year and Date: 2015-09-04
  • Int'l Joint Research
• [Presentation] 著しい下肢の過成長と部分的皮下脂肪組織の増殖を呈するPROS（PIK3CA-related Overgrowth Spectrum）の1例 (2015)
  • Author(s): 水野誠司, 榎戸靖, 森下剛, 花田直樹, 山田憲一郎, 若松延昭
  • Organizer: 第55回日本先天異常学会
  • Place of Presentation: 横浜
  • Year and Date: 2015-07-25
• [Presentation] Clinical and biochemical characterization of patients with HIBCH deficiency. (2015)
  • Author(s): Wakamatsu N, Yamada K, Naiki M, Hoshino S, Kitaura Y, Kondo Y, Nomura N, Kimura R, Fukushi D, Yamada Y, Shimozawa N, Yamaguchi S, Shimomura Y, Miura K
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20
• [Presentation] 家族性Xq28重複症候群の染色体重複機構の解明 (2014)
  • Author(s): 福士大輔、山田憲一郎、野村紀子ら
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-22
• [Presentation] チアミントランスポーター, SLC19A3欠損症とその病態解明 (2014)
  • Author(s): 若松延昭
  • Organizer: ビタミンB研究委員会 第438回研究協議会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-22
  • Invited
• [Presentation] HIBCH欠損症の同定と変異タンパク質の生化学的解析 (2014)
  • Author(s): 山田憲一郎、内木美紗子1、星野 伸ら
  • Organizer: 第56回日本先天代謝異常大会
  • Place of Presentation: 宮城
  • Year and Date: 2014-11-14
• [Presentation] HIBCH（3-Hydroxyisobutyryl-CoA hydrolase）欠損症の同定と変異タンパク質の生化学的解析 (2014)
  • Author(s): 山田憲一郎、内木美紗子、星野 伸ら
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
• [Presentation] 乳児期に緩徐に発症したSLC19A3遺伝子変異を有する1例. (2014)
  • Author(s): 村上智美, 渡邉誠司, 山田憲一郎ら
  • Organizer: 第61回静岡小児神経研究会
  • Place of Presentation: 浜松
  • Year and Date: 2014-07-05
• [Presentation] A case of siblings with Leigh-like disease caused by 3-hydroxyisobutyryl-CoA hydrolase deficiency. (2014)
  • Author(s): Yamada K, Naiki M, Hoshino S., et al.
  • Organizer: European Human Genetics Conference 2014
  • Place of Presentation: Milano, Italy
  • Year and Date: 2014-06-01
• [Book] 「神経症候群Ⅲ−その他の神経疾患を含めて−（第2版）」 HPRT欠損症（Lesch-Nyhan症候群、Kelley-Seegmiller症候群） (2014)
  • Author(s): 山田裕一，若松延昭
  • Total Pages: 4
  • Publisher: 日本臨床
• [Book] 「神経症候群Ⅳ−その他の神経疾患を含めて−（第2版）」 Mowat-Wilson症候群． (2014)
  • Author(s): 若松延昭，平木洋子
  • Total Pages: 5
  • Publisher: 日本臨床
• [Remarks] バリン代謝異常による小児の基底核疾患
  • URL: http://www.inst-hsc.jp/