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遺伝子医療研究部門

1 研究活動の概要・目的

遺伝子医療研究部門では、1)知的障害が見られる様々な疾患と自閉症スペクトラム障害の病因を同定し、2)疾患の発症機序や治療につながる知見を得て、3)臨床へ還元することを目的として、以下のような研究を行っています。①知的障害と自閉症スペクトラム障害の病因となる単一遺伝子の同定と変異解析、②染色体に重複、欠失、転座、逆位などの構造異常が見られる知的障害児・者の病因解明、③当部門で病因を同定した疾患のモデルマウスの作製とそれを用いた疾患の病態解明です

2 研究内容紹介

遺伝子医療研究部門では、前身の遺伝学部において2001年にコロニー中央病院で加療するモワット・ウィルソン症候群の症例の解析から、SIP1というタンパク質をコードするZEB2遺伝子が本症候群の病因遺伝子であることを世界で初めて明らかにし、論文発表しました。それ以来、国内外で本症候群と疑われた100例以上のZEB2遺伝子解析を行ってきました。2014年には、当部門で本症候群と確定診断した国内の40症例について、人口当たりの病気の出現頻度や症状の種類、ZEB2遺伝子変異の種類と病気の症状との相関をまとめた論文を発表しました。これらの研究成果をもとに、2015年に本症候群は厚生労働省の指定難病に認定されました。現在、患者やご家族、医療従事者向けに、本症候群に関する詳しい情報が難病情報センターのホームページで公開されています(指定難病178、モワット・ウィルソン症候群;http://www.nanbyou.or.jp/entry/4595)

そのほか、コロニー中央病院や他の医療機関との共同研究として、①病因不明の基底核疾患の症例を解析し、SLC19A3、HIBCH、ECHS1の3つの病因遺伝子を同定しました。現在、国内の病因不明の基底核疾患の症例について、SLC19A3とECHS1遺伝子の解析を行う体制を整えています。②過成長症候群のひとつであるPIK3CA-related overgrowth spectrum (PROS)の診断方法の開発と治療方法の検討を行いました。PI3K/AKT/mTOR経路の抑制を指標に治療薬の検討を行った結果、メトホルミンは、PI3K/AKT/mTOR経路の抑制効果があり、なおかつ正常細胞への影響が少ないため治療薬として有望であることを明らかにしました。③軽度知的障害と自閉症が見られ、de novoの染色体相互転座を伴う症例の転座断点部位の解析を行った結果、断点部位をSOX5遺伝子の中に同定し、本邦初のLamb-Shaffer症候群として誌上に発表しました。

3 メンバー紹介

部長  林 深 (はやし しん)
研究テーマ1:発達遅滞を伴う先天性異常疾患におけるゲノム構造異常・疾患原因遺伝子の探求
研究テーマ2:中枢神経異常を伴う発達遅滞における中枢神経の構造異常解析
主任研究員  山田憲一郎 (やまだ けんいちろう)
研究テーマ:モワット・ウィルソン症候群、SLC19A3欠損症、バリン代謝異常症
主任研究員  福士大輔 (ふくし だいすけ)
研究テーマ:染色体の構造異常が見られる知的障害の症例解析
研究員 河内 全 (こうち ぜん)
研究テーマ:発達障害を誘導する脳発達期におけるグリア細胞の恒常性破綻機序の解明
研究員  鈴木康予 (すずき やすよ)
研究テーマ:モワット・ウィルソン症候群、過成長症候群
研究員  加藤君子 (かとう きみこ)
研究テーマ:X連鎖性疾患、レット症候群
研究助手  野村紀子 (のむら のりこ)

4 活動内容

トピックス

・軽度知的障害と自閉症が見られ、de novoの染色体相互転座を伴う症例の転座断点部位の解析を行い、その研究成果を本邦初のLamb-Shaffer症候群としてGene誌に発表しました。(2018/4/11)

・過成長症候群のひとつであるPIK3CA-related overgrowth spectrum (PROS)の診断方法の開発と治療方法の検討を行い、その研究成果をOncotarget誌に発表しました。(2017/7/27)

・SLC19A3欠損症の病態解明とチアミンによる治療の効果を検証し、その研究成果をPLoS One誌に発表しました。(2017/7/26)

・2番染色体(2p24.3-pter)重複と5番染色体(5p14.3-pter)欠失を伴い、重度知的障害が見られる姉弟例の染色体転座断点部位の解析を行い、その研究成果をAm J Med Genet A誌に発表しました。(2017/7/26)

5 研究業績←クリックで表示

2019年

1 山田裕一:最新文献紹介「種々のアミロイド前駆タンパク質mRNA (APP-mRNA)アイソフォームの定量化と、レッシュ・ナイハン病におけるエピスタシス(遺伝子間相互作用)」.高尿酸血症と痛風 27: 80, 2019.

2018年

1 大澤彦太,谷口敦夫,関田千恵子,金子裕隆,市川奈緒美,瀬戸洋平,山中 寿,山田裕一:HPRT1欠損症9例の遺伝子解析.痛風と核酸代謝42 (1):123, 2018.

2 Fukushi D, Yamada K, Suzuki K, Inaba M, Nomura N, Suzuki Y, Katoh K, Mizuno S, Wakamatsu N: Clinical and genetic characterization of a patient with SOX5 haploinsufficiency caused by a de novo balanced reciprocal translocation. Gene 655:65-70, 2018.

2017年

1 Suzuki K, Yamada K, Fukuhara Y, Tsuji Y, Shibata K, Wakamatsu N: High-dose thiamine prevents brain lesions and prolongs survival of Slc19a3-deficient mice. PLoS One 12:e0180279, 2017.

2 Fukushi D, Kurosawa K, Suzuki Y, Suzuki K, Yamada K, Watanabe S, Yokochi K, Wakamatsu N: Clinical and molecular genetic characterization of two siblings with trisomy 2p24.3-pter and monosomy 5p14.3-pter. Am J Med Genet A 173A(8): 2201-2209, 2017.

3 Suzuki Y, Enokido Y, Yamada K, Inaba M, Kuwata K, Hanada N, Morishita T, Mizuno S, Wakamatsu N: The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS). Oncotarget 8: 45470-45483, 2017.

4 Teraishi M, Takaishi M, Nakajima K, Ikeda M, Higashi Y, Shimoda S, Asada Y, Hijikata A, Ohara O, Hiraki Y, Mizuno S, Fukada T, Furukawa T, Wakamatsu N, Sano S. Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular similarity between Mowat-Wilson syndrome and Ehlers-Danlos syndrome. Scientific Reports, 2017 Apr 19;7:46565. doi: 10.1038/srep46565.

5 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: Phenotype-genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties.Hum Mutat 38(7): 805-815, 2017.

6 山田裕一:核酸代謝異常症.日本臨牀別冊 新領域別症候群シリーズ No.37「精神医学症候群Ⅰ?その他の精神疾患を含めて?(第2版)」,日本臨牀社,pp. 177-182, 2017.

7 Ono H, Kurosawa K, Wakamatsu N, Masuda S :Hearing impairment in a female infant with interstitial deletion of 2q24.1q24.3.Ono H, Kurosawa K, Wakamatsu N, Masuda S: Hearing impairment in a female infant with interstitial deletion of 2q24.1q24.3. Congenit Anom (Kyoto) 57(4): 118-121, 2017.

2016年

1 山田裕一:先天性プリン代謝異常症.日本臨牀増刊号「高尿酸血症・低尿酸血症?最近の診断と治療?」, 日本臨牀社,74巻増刊号 9: 114-119, 2016.

2 Baba S, Saito T, Yamada Y, Takeshita E, Nomura N, Yamada K, Wakamatsu N, Sasaki M. Novel mutation in HPRT1 causing a splicing error with multiple variations. Nucleosides Nucleotides Nucleic Acids 36:1,1-6,2016.

2015年

1 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: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.痛風と核酸代謝 39(2): 121-128, 2015.

2 Takagi T, Nishizaki Y, Matsui F, Wakamatsu N, Higashi Y. 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. Hum Mol Genet 24:6390-6402, 2015.

3 山田裕一: Lesch-Nyhan症候群(HPRT欠損症).「今日の小児治療指針(第16版)」第6章 先天代謝異常,医学書院, pp 228-229, 2015

 

4 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: 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. J Med Genet 52: 691-698, 2015.

5 Hasegawa H, Shinohara Y, Nozaki S, Nakamura M, Oh K, Namiki O, Suzuki K, Nakahara A, Miyazawa M, Ishikawa K, Himeno T, Yoshida S, Ueda T, Yamada Y, Ichida K: Hydrophilic-interaction liquid chromatography tandem mass spectrometric determination of erythrocyte 5-phosphoribosyl 1-pyrophosphate in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency.J Chromatography B, 976-977: 55-60, 2015.

6 山田裕一:遺伝子変異診断.特集「痛風・核酸代謝における検査・診断法の進歩」,高尿酸血症と痛風 23 (1):30-36, 2015.

2014年

1 吉本武史,姫野隆洋,竹島慎一,音成秀一郎,山田憲一郎,山田裕一,栗山 勝:痙攣と精神運動遅滞を主訴としたhypoxanthine-guanine phosphoribosyltransferase 部分欠損症の一例. 臨床神経学 54: 892-896, 2014.

2 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, Wakamatsu N: Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis. Mol Genet Metab Rep 1: 455-460.

3 Suzuki Y, Jin C, Iwase T, Yazawa I: β-III Tubulin Fragments Inhibit α-Synuclein Accumulation in Models of Multiple System Atrophy. J Biol Chem 289:24374-24382.

4 Yamada Y, Nomura N, Yamada K, Kimura R, Fukushi D, Wakamatsu N, Matsuda Y, Yamauchi T, Ueda T, Hasegawa H, Nakamura M, Ichida K, Kaneko K, Fujimori S: Hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiencies: HPRT1 mutations in new Japanese families and PRPP concentration. Nucleosides Nucleotides Nucleic Acids 33: 218-222.

5 Kaneko K, Iwamoto H, Yasuda M, Inazawa K, Yamaoka N, Fukuuchi T, Tamura Y, Uchida S, Mawatari K, Nakagomi K, Yamada Y, Fujimori S: Proteomic analysis to examine the role of matrix proteins in a gouty tophus from a patient with recurrentgout. Nucleosides Nucleotides Nucleic Acids 33: 199-207.

6 山田裕一,若松延昭:HPRT欠損症(Lesch-Nyhan症候群、Kelley-Seegmiller症候群).別冊日本臨床 新領域別症候群シリーズ No.28「神経症候群Ⅲ?その他の神経疾患を含めて?(第2版)」, pp 632-636, 2014.06.20.

7 若松延昭,平木洋子:Mowat-Wilson症候群.別冊日本臨床 新領域別症候群シリーズ No.29「神経症候群Ⅳ?その他の神経疾患を含めて?(第2版)」, pp 613-616, 2014.09.20.

8 Yamada Y, Nomura N, Yamada K, Matsuo M, Suzuki Y, Sameshima K, Kimura R, Yamamoto Y, Fukushi D, Fukuhara Y, Ishihara N, Nishi E, Imataka G, Suzumura H, Hamano S, Shimizu K, Iwakoshi M, Ohama K, Ohta A, Wakamoto H, Kajita M, Miura K, Yokochi K, Kosaki K, Kuroda T, Kosaki R, Hiraki Y, Saito K, Mizuno S, Kurosawa K, Okamoto N, Wakamatsu N: The Spectrum of ZEB2 Mutations Causing the Mowat-Wilson Syndrome in Japanese Populations. Am J Med Genet A: 164A(8):1899-1908.

9 Naiki M, Ochi N, Kato YS, Purevsuren J, Yamada K, Kimura R, Fukushi D, Hara S, Yamada Y, Kumagai T, Yamaguchi S, Wakamatsu N: Mutations in HADHB, which Encodes the β-subunit of Mitochondrial Trifunctional Protein, Cause Infantile Onset Hypoparathyroidism and Peripheral Polyneuropathy. Am J Med Genet A: 164A(5):1180-1187.

10 Fukushi D, Yamada K, Nomura N, Naiki M, Kimura R, Yamada Y, Kumagai T, Yamaguchi K, Miyake Y, Wakamatsu N: Clinical Characterization and Identification of Duplication Breakpoints in a Japanese Family with Xq28 Duplication Syndrome Including MECP2. Am J Med Genet A: 164A(4):924-933.

2013年

1 Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O’Neill PJ, Jinnah HA for the Lesch-Nyhan Disease International Study Group: Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain (2014) 137: 1282-1303, first published online August 22, 2013.

2 Yamada K, Takado Y, Kato YS, Yamada Y, Ishiguro H, Wakamatsu N: Characterization of the mutant β-subunit of β-hexosaminidase for dimer formation responsible for the adult form of Sandhoff disease with the motor neuron disease phenotype. J Biochem 153: 111-119, 2013.

3 山田裕一,若松延昭:HPRT欠損症の原因となる新たなHPRT1遺伝子変異.痛風と核酸代謝37: 63, 2013

4 山田裕一:HPRT欠損症(Lesch-Nyhan症候群).先天代謝異常ハンドブック(中山書店),Ⅱ各論, 12章プリン・ピリミジン代謝異常,遠藤文雄 編,pp 282-283, 2013.

5 山田裕一:HGPRTaseの遺伝子異常と女児例の発見.特集「日本が貢献した世界的新知見」,高尿酸血症と痛風 21 (1): 27-32, 2013.

6 山田裕一,若松延昭:遺伝病診療:HPRT欠損症診断.「核酸代謝の研究はいかに生命科学の発展に寄与したか」.痛風と核酸代謝36: 134, 2013.

7 山田裕一:先天性プリン代謝異常症に関わる2酵素 (HPRT, PRPPS)の遺伝子解析.痛風財団平成23年度研究助成に対する概要報告書 27: 8, 2013.

2012年

1 Yamada K, Nomura N, Yamano A, Yamada Y, Wakamatsu N. Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development. Gene 492: 270-275, 2012.

2 Naiki M, Mizuno S, Yamada K, Yamada Y, Kimura R, Oshiro M, Okamoto N, Makita Y, Seishima M, Wakamatsu N: MBTPS2 mutation causes BRESEK/BRESHECK syndrome. Am J Med Genet A, 158A: 97-102, 2012.

3 Fukushi D, Mizuno S, Yamada K, Kimura R, Yamada Y, Kumagai T, Wakamatsu N: Aneuploidy and intellectual disability. in Aneuploidy in Health and Disease, Storchova Z ed, InTech-Open Access Publisher (Rijeka, Croatia), pp 107-122, 2012.

4 山田裕一:PRPP合成酵素遺伝子PRPS1の遺伝子異常に起因する4つの症候群.痛風と核酸代謝36: 1-8, 2012.

5 山田裕一:ヒポキサンチン-グアニンホスホリボシルトランスフェラーゼ欠損症.別冊 日本臨床 新領域別症候群シリーズ No.19「先天代謝異常症候群(第2版)-病因・病態研究.診断治療の進歩-」(上),pp 573-583, 2012.

2011年

1 Mizuno S, Fukushi D, Kimura R, Yamada K, Yamada Y, Kumagai T, Wakamatsu N: Clinical and genomic characterization of sibling with a distal duplication of chromosome 9q [9q34.1-qter]. Am J Med Genet A, 155A: 2274-2280, 2011.

2 Mutoh N, Kitajima S, Ichihara S: Apoptotic cell death in the fission yeast Schizosacchamyces pombe indused by valprotid acid and its extreme susceptibility to pH change. Biosci Biotechnol Biochem 75: 1113-1118, 2011.

3 Kaneko K, Yoshida N, Okazaki K, Yamanobe T, Hachisu H, Yamaoka N, Yasuda M, Ogata N, Yamada Y, Uchida S, Fujimori S: Urinary stone analysis in a patient with hyperuricemia to determine the mechanism of stone formation. Nucleosides Nucleotides Nucleic Acids 30: 1072-1076, 2011.

4 Yamada Y, Wakamatsu N, Taniguchi A, Kaneko K, Fujimori S: Hypoxanthine guanine phosphoribosyltransferase (HPRT) mutations in Asian population. Nucleosides Nucleotides Nucleic Acids 30: 1248-1255, 2011.

5 Yamaoka N, Inazawa K, Inagawa S, Fujimori S, Yasuda M, Mawatari K, Nakagomi K, Yamada Y, Kaneko K: Simultaneous determination of purine and pyrimidine metabolites in HPRT-deficient cell lines. Nucleosides Nucleotides Nucleic Acids 30: 1256-1259, 2011.

6 Taniguchi1 A, Yamada Y, Hakota M, Sekita C, Kawamoto M, Kaneko H, Yamanaka H: Molecular characterization of deletion in the HPRT gene in a patient with Lesch-Nyhan syndrome. Nucleosides Nucleotides Nucleic Acids 30: 1266-1271, 2011.

7 Yamada Y, Yamada K, Nomura N, Yamano A, Kimura R, Naiki M, Fukushi D, Wakamatsu N, Taniguchi A, Kaneko K, Fujimori S: Molecular analysis of X-linked inborn errors of purine metabolism: HPRT1 and PRPS1 mutations. Nucleosides Nucleotides Nucleic Acids 30: 1272-1275, 2011.

2010年

1 Yamada Y, Yamada K, Nomura N, Yamano A, Kimura R, Tomida S, Naiki M, Wakamatsu N: Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism. Nucleosides Nucleotides Nucleic Acids 29: 291-294, 2010.

2 Yamaoka N, Kaneko K, Kudo Y, Aoki M, Yasuda M, Mawatari K, Nakagomi K, Yamada Y, Yamamoto T: Analysis of purine in purine-rich cauliflower. Nucleosides Nucleotides Nucleic Acids 29: 518-521, 2010.

3 Yamada K, Fukushi D, Ono T, Kondo Y, Kimura R, Nomura N, Kosaki K, Yamada Y, Mizuno S, Wakamatsu N: Characterization of a de novo balanced t(4;20)(q33;q12) translocation in a patient with mental retardation. Am J Med Genet A, 152A: 3057-3057, 2010.

4 Yamada K, Miura K, Hara K, Suzuki M, Nakanishi K, Kumagai T, Ishihara N, Yamada Y, Kuwano R, Tsuji S, Wakamatsu N: A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations. BMC Medical Genetics 11:171, doi:10.1186/1471-2350-11-171, 2010.

5 山田裕一:核酸代謝異常(Lesch-Nyhan症候群など).小児科診療-増刊号「特集小児の治療指針」,73 (suppl): 520-522, 2010.

2001年~2009年

1 Lyle R, Bena F1, Gagos S, Gehrig C, Lopez G, Schinzel A, Lespinasse J, Bottani A, Dahoun S, Taine L3, Doco-Fenzy M, Cornillet-Lefebvre P, Pelet A, Lyonnet S, Toutain A, Colleaux L, Horst J, Kennerknecht I, Wakamatsu N, Descartes M, Franklin JC, Florentin-Arar L, Kitsiou S, Ait Yahya-Graison E, Costantine M, Sinet PM, Delabar JM, Antonarakis SE: Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. Eur J Hum Genet 17: 454-466, 2009

2 Garavelli L, Zollino M, Cerruti Mainardi P, Gurrieri F, Rivieri F, Soli F, Verri R, Albertini E, Favaron E, Zignani M, Orteschi D, Bianchi P, Faravelli P, Forzano F, Seri M, Wischmeijer A, Turchetti D, Pompilii E, Gnoli M, Cocchi G, Mazzanti E, Bergamaschi R, De Brasi D, Sperandeo MP, Mari F, Uliana V, Mostardini R, Cecconi M, Grasso M, Sassi S, Sebastio G, Renieri A, Silengo M, Bernasconi S, Wakamatsu N, Neri G: Mowat-Wilson syndrome: facial phenotype changing with age. Study of 19 Italian patients and review of the others literature. Am J Med Genet 149A: 417-426, 2009.

3 Fukushi D, Watanabe N, Kasai F, Haruta M, Kikuchi A, Kikuta A, Kato K,Nakadate H, Tsunematsu Y, Kaneko Y: Centrosome amplification is correlated with ploidy divergence, but not with MYCN amplification, in neuroblastomatumors. Cancer Genet Cytogenet 188:32-41, 2009

4 山田裕一:HPRT欠損症.「特集:高尿酸血症・痛風Update」.日本臨牀66: 687-693, 2008.

5 Yamada Y, Nomura N, Yamada K, Wakamatsu N, Kaneko K, Fujimori: Molecular analysis of HPRT deficiencies: novel mutations and the spectrum of Japanese mutations. Nucleosides Nucleotides Nucleic Acids 27: 570-574, 2008.

6 Ishida Y, Ishimaru A, Tauchi H, Yamaguchi A, Yokoyama M, Hiroi K, Wakamatsu N, Yamada Y : Partial hypoxanthine-guanine phosphoribosyltransferase deficiency due to a newly recognized mutation presenting with renal failure in a one-year-old boy. Eur J Pediatr 167: 957-959, 2008.

7 Mutoh N, Kitajima S: Accelerated chronological aging of a mutant fission yeast deficient in both glutathione and superoxide dismutase having Cu and Zn as cofactors and its enhancement by Sir2 deficiency. Biosci Biotech Biochem 71: 2841-2844, 2007.

8 山田裕一,野村紀子,若松延昭:HPRT欠損症の遺伝子解析:新たな6変異とアジア人変異の総括.痛風と核酸代謝 31: 31-40, 2007.

9 小野教夫,木村礼子,山田憲一郎,若松延昭:見えない染色体異常 -染色体構築と分配機構の異常による先天性疾患.実験医学 25: 776-781, 2007.

10 Yamada Y, Nomura N, Yamada K, Wakamatsu N: Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian mutations with novel mutations. Mol Genet Metab 90: 70-76, 2007.

11 Kimura R, Takeshima K, Mizuno S, Kosaki K, Machida J, Kamamoto M, Muro Y, Shimosato K, Wakamatsu N, Sonta S, OnoT: Monopolar preparation of human lymphocytes for evaluation of the metaphase chromosome alignment. Chromosome Science 9: 75-83, 2006.

12 Ono T: Key roles of condensins in mitotic chromosome assembly and segregation. Chromosome Science 9: 33-45, 2006.

13 Yamada Y, Wakamatsu N: Molecular analysis of hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment, Moriwaki Y ed, Research Signpost, Kerala, pp 15-27, 2006.

14 Kondo Y, Mizuno S, Ohara K, Nakamura T, Yamada K, Yamamori S, Hayakawa C, Ishii T, Yamada Y, Wakamatsu N: Two cases of partial trisomy 21 (pter-q22.1) without the major features of Down syndrome. Am J Med Genet 140A: 227-232. 2006.

15 Mutoh N, Kawabata M, Kitajima S: Effects offour oxidants, menadione, 1-chloro-2,4-dinitrobenzene, hydrogen peroxide and cumene hydroperoxide, on fission yeastSchizosaccharmoyces pombe. J Biochem 138: 797-804, 2005. 16 Ishihara N, Shimada A, Kato J, Niimi N, Tanaka S, Miura K, Suzuki T, Wakamatsu N, Nagaya M: Variations in aganglionic segment length of the enteric neural plexus in Mowat-Wilson syndrome. J Pediatr Surg 40:1411-1419, 2005.

17 Mizuno S, Yamada Y, Yamada K, Nomura N, Wakamatsu N: Clinical variability in a Japanese hereditary lymphedema type I family with an FLT4 mutation. Cong Anom 45: 59-61, 2005.

18 Mutoh N, Kawabata M, Nakagawa CW, Kitajima S: Pro-oxidant action of phloxine B on fission yeast Schizosaccharomyces pombe. Yeast 22: 91-97, 2005.

19 Ono T, Fang Y, Spector DL, Hirano T: Spatial and temporal regulation of condensins I and II in mitotic chromosome assembly in human cells. Mol Biol Cell 15: 3296-3308, 2004.

20 Yamada Y, Yamada K, Sonta S, Wakamatsu N, Ogasawara N: Mutations in the hypoxanthine guanine phosphoribosyltransferase gene (HPRT1) in Asian HPRT deficient families. Nucleosides Nucleotides Nucleic Acids 23: 1169-1172, 2004.

21 Mizunuma M, Yamada Y, Yamada K, Sonta S, Wakamatsu N, Kaneko K, Ogasawara N, Fujimori S: Disruption in the hypoxanthine phosphoribosyltransferase gene caused by translocation in a patient with Lesch-Nyhan syndrome. Nucleosides Nucleotides Nucleic Acids 23: 1173-1176, 2004.

22 Ishihara N, Yamada K, Yamada Y, Miura K, Kato J, Kuwabara N, Hara Y, Kobayashi Y, Hoshino K, Nomura Y, Mimaki M, Ohya K, Matsushima M, Nitta H, Tanaka K, Segawa M, Ohki T, Ezoe T, Kumagai T, Onuma A, Kuroda T, Yoneda M, Yamanaka T, Saeki M, Segawa M, T Saji, Nagaya M, WakamatsuN: Clinicaland molecular analysis of Mowat-Wilson syndrome associated with ZFHX1Bmutations and deletions at 2q22-q24.1. J Med Genet 41: 387-394, 2004.

23 Silengo M, Ferrero GB, Wakamatsu N: Pachygyria and cerebellar hypoplasia in a patient with a 2q22-q23 deletion that includes the ZFHX1B gene. Am J Med Genet 127A: 109, 2004

24 Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T: Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell 115: 109-121, 2003.

25 Nagaya M, Kato J, Niimi, N, Tanaka S, Wakamatsu N: Clinical feature of a form of Hirschspurung’s disease caused by a novel genetic abnormality. J Pediar Surg 37: 1117-1122, 2002.

26 Mutoh N, Nakagawa CW, Yamada K: Characterization of Cu, Zn superoxide dismutase deficient mutant of fission yeast Schizosaccharomyces pombe. Curr Genet 41: 82-88, 2002

27 Yoneda M, Fujita T, Yamada Y, Yamada K, Fujii A, Inagaki T, Nakagawa H, Kishikawa M, Shimada A, Nagaya M, Azuma T, Kuriyama M, Wakamatsu N: Late infantile Hirschsprung disease-mental retardation syndrome with a 3-bp deletion in ZFHX1B. Neurology 59: 1637-1640, 2002.

28 Isoai A, Kimura H, Reichert A, Schorgendorfer K, Nikaido K, Tohda H, Giga-Hama Y, Mutoh N, Kumagai H: Production of D-amino acid oxidase (DAO) of Trigonopsis variabilis in Schizosaccharomyces pombe, and the characterization of biocatalysts prepared with recombinant cells. Biotechnol Bioeng 80: 22-32, 2002.

29 Yamada H, Adachi T, Fukatsu A, Misao S, Yamada Y, Aoki T, Miura N, Sakuma M, Nishikawa K, Futenma A, Kakumu S: Extracellular superoxide dismutase and glomerular cells: its production and regulation. FEBS Lett 519: 77-81, 2002.

30 Yamada K, Yamada Y, Nomura N, Miura K, Wakako R, Hayakawa C, Matsumoto A, Kumagai T, Yoshimura I, Miyazaki S, Kato K, Sonta S, Ono H, Yamanaka T, Nagaya M, Wakamatsu N: Nonsense and frameshift mutations in ZFHX1B, encoding Smad-Interacting protein 1, cause a complex developmental disorder with a great variety of clinical features. Am J Hum Genet 69: 1178-1185, 2001.

31 Wakamatsu N, Yamada Y, Yamada K, Ono T, Nomura N, Taniguchi H, Kitoh H, Mutoh N, Yamanaka T1, Mushiake K, Kato K, Sonta S, Nagaya M: Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. Nat Genet 27: 369-370, 2001.

32 Ono T, Kondoh Y, Kagiyama N, Sonta S, Yoshida MC: Genomic organization and chromosomal distribution of rat ID elements. Genes Genet Syst 76: 213-220, 2001.

33 Ono T, Sonta S: Chromosome map of cosmid clones constructed with Chinese hamster genomic DNA. Cytogenet Cell Genet 95: 97-102, 2001.

34 Machida J, Yamada Y, Ogasawara N, Kaetsu A, Yamamoto T: Lesch-Nyhan syndrome: Case report and genetic study of one Japanese family. Asian J Oral Maxillofac Surg 13: 111-115, 2001.

35 Yamada Y, Miura K, Kumagai T, Hayakawa C, Miyazaki S, Matsumoto A, Kurosawa K, Nomura N, Taniguchi H, Sonta S, Yamanaka T, Wakamatsu N: Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation. Hum Mutat (Online#443) 18: 253, 2001.