国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

代表: 03-3416-0181 / 予約センター(病院): 03-5494-7300
〈月~金曜日(祝祭日を除く)9時〜17時〉

  • アクセス・交通案内
  • 予約センター
  • MENU

研究者・企業の方へ Scholar & Enterprise

研究者・企業の方へ Scholar & Enterprise

分子内分泌研究部

研究部紹介

胎児期から生殖年齢期までの内分泌疾患、成長障害、および先天奇形症候群を主な対象として、分子遺伝学的・臨床的解析を行っています。これにより、新たな疾患発症機序の解明、臨床像や予後の解明、現行の治療法の効果の判定、迅速かつ正確な診断法の確立、新しい治療法の開発を目指しています。
内分泌(ホルモン分泌)機構の異常は、成長障害、性分化疾患、性成熟異常、先天奇形症候群、生殖機能障害などさまざまな疾患を招きます。これらの疾患の発症機序には未解明の点が多く、有効な診断法や治療法が確立されていない疾患が多く存在します。分子内分泌研究部では、国内外の臨床医や研究者と連携し、内分泌疾患の臨床的および分子遺伝学的研究を行っています。
私たちの研究の目的は、新規疾患発症遺伝子の発見、疾患成立機序の解明、疾患重症化因子の解明、診断法や治療法の開発などを介して、よりよい医療の実現と健全な次世代の育成に貢献することです。

○研究部問い合わせ窓口

深見 真紀
深見真紀のメールアドレスの画像

○臨床検体の遺伝子解析について

分子内分泌研究部では、研究の一環として性分化疾患、成長障害、性成熟疾患、カルシウム異常症などの遺伝子診断を行っています。研究の詳細や検体受け入れの可否については、主治医から下記メールアドレスに問い合わせ下さい。
問い合わせ先のメールアドレスの画像

研究内容

  1. 単一遺伝子疾患研究:性分化・性成熟疾患、成長障害、先天奇形症候群などを対象として、新規疾患成立機序の解明、既知責任遺伝子の遺伝子型-表現型による臨床像の決定、重症度修飾因子の解明、現行の治療法の効果判定、新たな治療法の開発を目指しています。
  2. インプリンティング疾患・エピジェネティクス疾患研究:14番染色体ダイソミー症候群やシルバーラッセル症候群など、ヒトインプリンティング疾患の疾患成立機序の解明とそれに基づく治療法の開発、疾患重症度決定因子の解明を行っています。また、生殖補助医療におけるインプリンティング異常発症リスクの評価を行っています。
  3. 多因子疾患研究:小児期発症1型糖尿病、多嚢胞性卵巣症候群を含むさまざまな内分泌疾患、先天奇形症候群の発症に関与する環境因子、感受性多型の同定を行っています。
  4. 医療・社会への貢献:効率的遺伝子診断技術の提供、日本人患者の臨床データの集積、小児難治性疾患における診断・治療指針の作成などを通じて、社会に貢献しています。
さらに、以下の共同研究を行っています。
  • 臨床検体の集積:国内外の80以上の医療機関と連携し、さまざまな疾患の臨床検体を集積しています。これらの検体のゲノム・エピゲノム解析により新たな疾患発症機序を解明します。

  • 遺伝子診断システムの構築:全国の研究施設、医療機関、NPO法人等と連携し、持続可能な遺伝子解析技術提供を目指した基盤づくりに取り組んでいます。

  • 遺伝子機能の解明:国内外の基礎研究者と連携して、成育疾患発症に関与する遺伝子相互作用の解明を行っています。

スタッフ

分子内分泌研究部

臨床内分泌研究室

基礎内分泌研究室

部室員

  • 福井 由宇子(特任研究員)
  • 勝又 規行(研究員)
  • 松原 圭子(研究員)
  • 宮戸 真美(研究員)
  • 綾部 匡之(研究員)
  • 奥野 美佐子(研究員)
  • 中村 繁(研究員)
  • 服部 淳(研究員)
  • 斎藤 和毅(大学院生)
  • 島 彦仁(大学院生)
  • 勝見 桃理(大学院生)
  • 井上 毅信(大学院生)
  • 牛嶋 規久美(大学院生)
  • 鈴木 江莉奈(研究補助員)
  • 神野 智子(研究補助者)
  • 丹治 玉江(研究補助者)
  • 三代川 温子(研究補助者)
  • 金子 晶子(研究補助者)
  • 五十嵐 暁子(事務補助者)
  • 山﨑 久美(事務補助者)
  • 福田 るみ子(事務補助者)

業績

2015

  1. Kagami M, Mizuno S, Matsubara K, Nakabayashi K, Sano S , Fuke T, Fukami M , Ogata T. Epimutations of the IG-DMR and the MEG3-DMR at the 14q32.2 imprinted region in two patients with Silver-Russell syndrome-compatible phenotype. European Journal of Human Genetics 2015 [Epub ahead of print]
  2. Izumi Y, Musha I, Suzuki E, Iso M, Jinno T, Horikawa R, Amemiya S, Ogata T, Fukami M, Ohtake A. Hypogonadotropic hypogonadism in a female patient previously diagnosed as having Waardenburg syndrome due to a SOX10 mutation. ENDOCRINE 49:553–556, 2015
  3. Nakashima S, Kato F, Kosho T, Nagasaki K, Kikuchi T, Kagami M, Fukami M, Ogata T. Silver-Russell syndrome without body asymmetry in three patients with duplications of maternally derived chromosome 11p15 involving CDKN1C. Journal of Human Genetics 60(2):91–95, 2015
  4. Saito K, Miyado M, Kobori Y, Tanaka Y, Ishikawa H, Yoshida A, Katsumi M, Saito H, Kubota T, Okada H, Ogata T, Fukami M. Copy-Number Variations in Y Chromosomal Azoospermia Factor Regions Identified by Multiplex Ligation-Dependent Probe Amplification. Journal of Human Genetics 60(3):127–131, 2015
  5. Igarashi M, Wada Y, Kojima Y, Miyado M, Nakamura M, Muroya K, Mizuno K, Hayashi Y, Nonomura K, Kohri K, Ogata T, Fukami M. Novel Splice Site Mutation in MAMLD1 in a Patient with Hypospadias. Sexual Development 2015 [Epub ahead of print]
  6. Kon M, Suzuki E, Dung VC, Hasegawa Y, Mitsui T, Muroya K, Ueoka K, Igarashi N, Nagasaki K, Oto Y, Hamajima T, Yoshino K, Igarashi M, Kato-Fukui Y, Nakabayashi K, Hayashi K, Hata K, Matsubara Y, Moriya K, Ogata T, Nonomura K, Fukami M. Molecular basis of non-syndromic hypospadias: Systematic mutation screening and genome-wide copy-number analysis of 62 patients. Human Reproduction 30(3):499–506, 2015
  7. Igarashi M, Mikami H, Katsumi M, Miyado M, Izumi Y, Ogata T, Fukami M. SOX3 Overdosage Permits Normal Sex Development in Females with Random X Inactivation. Sexual Development 2015 [Epub ahead of print]
  8. Katsumi M, Ishikawa H, Tanaka Y, Saito K, Kobori Y, Okada H, Saito H, Nakabayashi K, Matsubara Y, Ogata T, Fukami M, Miyado M. Microhomology-Mediated Microduplication in the Y Chromosomal Azoospermia Factor a (AZFa) Region in a Male with Mild Asthenozoospermia. Cytogenetics and Genome Research 144(4):285–289, 2015
  9. Ruiz-Arana IL, Hübner A, Cetingdag C, Krude H, Grüters A, Fukami M, Biebermann H, Köhler B. A Novel Hemizygous Mutation of MAMLD1 in a Patient with 46,XY Complete Gonadal Dysgenesis. Sexual Development 2015 [Epub ahead of print]
  10. Yagi H, Takagi M, Kon M, Igarashi M, Fukami M, Hasegawa Y. Fertility preservation in a family with a novel NR5A1 mutation. Endocrine Journal. [Epub ahead of print]
  11. Okuno M, Ogata T, Nakabayashi K, Urakami T, Fukami M, Nagasaki K. Endocrinopathies in a Boy with Cryptic Copy-number Variations on 4q, 7q, and Xp. Human Genome Variation. [Epub ahead of print]
  12. Sano S, Iwata H, Matsubara K, Fukami M, Kagami M, Ogata T. Growth hormone deficiency in monozygotic twins with autosomal dominant pseudohypoparathyroidism type Ib. Endocrine Journal 62(6):523–529, 2015
  13. Suzuki E, Izumi Y, Chiba Y, Horikawa R, Matsubara Y, Tanaka M, Ogata T, Fukami M, Naiki Y. Loss-of-Function SOX10 Mutation in a Patient with Kallmann Syndrome, Hearing Loss, and Iris Hypopigmentation. Hormone Research in Pediatrics. [Epub ahead of print]
  14. Katoh-Fukui Y, Igarashi M, Nagasaki K, Horikawa R, Nagai T, Tsuchiya T, Suzuki E, Miyado M, Hata K, Nakabayashi K, Hayashi K, Matsubara Y, Baba T, Morohashi K, Igarashi A, Ogata T, Takada S, Fukami M. Testicular Dysgenesis/Regression without Campomelic Dysplasia in Patients Carrying Missense Mutations and Upstream Deletion of SOX9. Molecular Genetics and Genome Medicine [Epub ahead of print]
  15. Fukami M, Naiki Y, Muroya K, Hamajima T, Soneda S, Horikawa R, Jinno T, Katsumi M, Nakamura A, Asakura Y, Adachi M, Ogata T, Kanzaki S; Japanese SHOX study group.Rare pseudoautosomal copy-number variations involving SHOX and/or its flanking regions in individuals with and without short stature. Journal of Human Genetics. 2015 [Epub ahead of print]
  16. Matsubara K, Kagami M, Nakabayashi K, Hata K, Fukami M, Ogata T, Yamazawa K. Exploration of hydroxymethylation in Kagami-Ogata syndrome caused by hypermethylation of imprinting control regions. Clinical Epigenetics 2015 [Epub ahead of print]

2014

  1. Fukami M, Suzuki J, Nakabayashi K, Tsunasima R, Ogata T, Shozu M, Noguchi S. Lack of Genomic Rearrangements Involving the Aromatase Gene CYP19A1 in Breast Cancer. Breast Cancer. 21(3):382-385, 2014
  2. Shihara D, Miyado M, Nakabayashi K, Shozu M, Ogata T, Nagasaki K, Fukami M. Aromatase excess syndrome in a family with upstream deletion of CYP19A1. Clinical Endocrinology. 81(2):314-316, 2014
  3. Tsuchiya T, Shibata M, Numabe H, Jinno T, Nakabayashi K, Nishimura G, Nagai T, Ogata T, Fukami M. Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestations of Langer mesomelic dysplasia. American Journal of Medical Genetics Part A. 164A(2):505-510, 2014
  4. Nagasaki K, Asami T, Sato H, Ogawa Y, Kikuchi T, Saitoh A, Ogata T, Fukami M. Long term follow up study for a patient with Floating-Harbor syndrome due to a hotspot SRCAP mutation. American Journal of Medical Genetics Part A. 164A(3):731-735, 2014
  5. Suzuki E, Yatsuga S, Igarashi M, Miyado M, Nakabayashi K, Hayashi K, Hata K, Umezawa A, Yamada G, Ogata T, Fukami M. De Novo Frameshift Mutation in Fibroblast Growth Factor 8 in a Male Patient with Gonadotropin Deficiency. Hormone Research in Paediatrics. 81(2):139-144, 2014
  6. Saito R, Yamamoto Y, Goto M, Araki S, Kubo K, Kawagoe R, Kawada Y, Kusuhara K, Igarashi M, Fukami M. Tamoxifen Treatment for Pubertal Gynecomastia in Two Siblings with Partial Androgen Insensitivity Syndrome. Hormone Research in Paediatrics. 81(3):211-216, 2014
  7. Sasaki A, Sumie M, Wada S, Kosaki R, Kurosawa K, Fukami M, Sago H, Ogata T, Kagami M. Prenatal genetic testing for a microdeletion at chromosome 14q32.2 imprinted region leading to UPD(14)pat-like phenotype. American Journal of Medical Genetics Part A. 164A(1):264-266, 2014
  8. Kato F, Hamajima T, Hasegawa T, Amano N, Horikawa R, Nishimura G, Nakashima S, Fuke T, Sano S, Fukami M, Ogata T. IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients. Clinical Endocrinology. 80(5):706-713, 2014
  9. Abe Y, Nagasaki K, Watababe T, Abe T, Fukami M. Association between compound heterozygous mutations of SLC34A3 and hypercalciuria. Hormone Research in Paediatrics. 2014 [Epub ahead of print]
  10. Ogata T, Niihori T, Tanaka N, Kawai M, Nagashima T, Funayama R, Nakayama K, Nakashim S, Kato F, Fukami M, Aoki Y, Matsubara Y. TBX1 Mutation Identified by Exome Sequencing in a Japanese Family with 22q11.2 Deletion Syndrome-like Craniofacial Features and Hypocalcemia. PLOS ONE. 9(3):e91598, 2014
  11. Matsubara K, Kataoka N, Ogita S, Sano S, Ogata T, Fukami M, Katsumata N. Uniparental disomy of chromosome 8 leading to homozygosity of a CYP11B1 mutation in a patient with congenital adrenal hyperplasia: Implication for a rare etiology of an autosomal recessive disorder. Endocrine Journal. 61(6):629-633, 2014
  12. Suzuki J, Azuma N, Dateki S, Soneda S, Muroya K, Yamamoto Y, Saito R, Sano S, Nagai T, Wada H, Endo A, Urakami T, Ogata T, Fukami M. Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities. Journal of Human Genetics. 59(6):353-356, 2014
  13. Izumi Y, Suzuki E, Kanzaki S, Yatsuga S, Kinjo S, Igarashi M, Maruyama T, Sano S, Horikawa R, Sato N, Nakabayashi K, Hata K, Umezawa A, Ogata T, Yoshimura Y, Fukami M. Genome-wide copy number analysis and systematic mutation screening in 58 patients with hypogonadotropic hypogonadism. Fertility and Sterility. 102(4):1130-1136, 2014
  14. Inui M, Miyado M, Igarashi M, Tamano M, Kubo A, Yamashita S, Asahara H, Fukami M, Takada S. Rapid generation of mouse models with defined point mutations by the CRISPR/Cas9 system. Scientific Reports. 4:5396, 2014
  15. Nakashima S, Ohishi A, Takada F, Kawamura H, Igarashi M, Fukami M, Ogata T. Clinical and molecular studies in four patients with SRY-positive 46,XX testicular disorders of sex development: implications for variable sex development and genomic rearrangements. Journal of Human Genetics. 2014 [Epub ahead of print]
  16. Izumi Y, Musha I, Suzuki E, Iso M, Jinno T, Horikawa R, Amemiya S, Ogata T, Fukami M, Ohtake A. Hypogonadotropic hypogonadism in a female patient previously diagnosed as having Waardenburg syndrome due to a SOX10 mutation. Endocrine. 2014 in press
  17. Nagata E, Hiroki Kano H, Kato F, Yamaguchi R, Nakashima S, Takayama S, Kosaki R, Tonoki H, Mizuno S, Watanabe S, Yoshiura K-I, Kosho T, Hasegawa T, Kimizuka M, Suzuki A, Shimizu K, Ohashi H, Haga N, Numabe H, Horii E, Nagai T, Yoshihashi H, Nishimura G, Toda T, Takada S, Yokoyama S, Asahara H, Sano S, Fukami M, Ikegawa S, Ogata T. Japanese founder duplications/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gollop-Wolfgang complex. Orphanet Journal of Rare Diseases. 9:125,2014
  18. Kon M, Suzuki E, Dung VC, Hasegawa Y, Mitsui T, Muroya K, Ueoka K, Igarashi N, Nagasaki K, Oto Y, Hamajima T, Yoshino K, Igarashi M, Kato-Fukui Y, Nakabayashi K, Hayashi K, Hata K, Matsubara Y, Moriya K, Ogata T, Nonomura K, Fukami M. Molecular basis of non-syndromic hypospadias: Systematic mutation screening and genome-wide copy-number analysis of 62 patients. Human Reproduction. 2014 [Epub ahead of print]
  19. Miyake Y, Tanaka K, Nishikawa T, Naruse M, Takayanagi R, Sasano H, Takeda Y, Shibata H, Sone M, Satoh F, Yamada M, Ueshiba H, Katabami T, Iwasaki Y, Tanaka H, Tanahashi Y, Suzuki S, Hasegawa T, Katsumata N, Tajima T, Toshihiko Yanase T. Prognosis in patients with primary aldosteronism in Japan: results from a nationwide epidemiological study. Endocrine Journal. 61(1):35-40, 2014
  20. Yoshizawa-Ogasawara A, Katsumata N, Horikawa R, Satoh M, Urakami T, Tanaka T. Third-generation aromatase inhibitor Improved adult height in a Japanese boy with testotoxicosis. Clinical Pediatric Endocrinology 23(2): 53–58, 2014
  21. Takasawa K, Ono M, Hijikata A, Matsubara Y, Katsumata N, Takagi M, Morio T, Ohara O, Kashimada K, Mizutani S. Two novel HSD3B2 missense mutations with diverse residual enzymatic activities for Δ5-steroids. Clinical endocrinology (Oxford). 80(6):782-789, 2014
  22. Kosaki R, Takenouchi T, Takeda N, Kagami M, Nakabayashi K, Hata K, Kosaki K. Somatic CTNNB1 mutation in hepatoblastoma from a patient with Simpson-Golabi-Behmel syndrome and germline GPC3 mutation. American Journal of Medical Genetics Part A. 164A(4):993-997, 2014
  23. Maeda T, Higashimoto K, Jozaki K, Yatsuki H, Nakabayashi K, Makita Y, Tonoki H, Okamoto N, Takada F, Ohashi H, Migita M, Kosaki R, Matsubara K, Ogata T, Matsuo M, Hamasaki Y, Ohtsuka Y, Nishioka K, Joh K, Mukai T, Hata K, Soejima H. Comprehensive and quantitative multilocus methylation analysis reveals the susceptibility of specific imprinted differentially methylated regions to aberrant methylation in Beckwith-Wiedemann syndrome with epimutations. Genetics in Medicine 16(12):903-912, 2014
  24. Kawano N, Miyado K, Yoshii N, Kanai S, Saito H, Miyado M, Inagaki N, Odawara Y, Hamatani T, Umezawa A. Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition. Scientific Reports. 4:4701, 2014
  25. Igarashi M, Hippo Y, Ochiai M, Fukuda H, Nakagama H. Akt is critically involved in cooperation between obesity and the dietary carcinogen amino-1-methyl-6-phenylimidazo [4,5-b] (PhIP) in rats. Biochemical and Biophysical Research Communications. 17(443):852-857, 2014
  26. Fukami M, Miyado M, Nagasaki K, Shozu M, Ogata T. Aromatase excess syndrome: A rare autosomal dominant disorder leading to pre- or peri-pubertal onset gynecomastia. Pediatric Endocrinology Reviews 11(3):298-305, 2014
  27. Shozu M, Fukami M, Ogata T. Understanding the pathological manifestations of aromatase excess syndrome: lessons for the clinic. Expert Review of Endocrinology and Metabolism 2014
  28. Seki A, Jinno T, Suzuki E, Takayama S, Ogata T, Fukami M. Skeletal deformity associated with SHOX deficiency. Clinical Pediatric Endocrinology 23(3):65-72, 2014

2013

  1. HigashimotoK, Jozaki K,Kosho T,Matsubara K, FukeT, Yamada D, YatsukiH, Maeda T, OhtsukaY, NishiokaK, Joh K, Koseki H, Ogata T,SoejimaH. A novel de novo point mutation of the OCT-binding site in theIGF2/H19-imprinting control region in a Beckwith-Wiedemannsyndrome patient. Clinical Genetics. 86(6):539-544, 2013
  2. KatohM, IgarashiM, Fukuda H, NakagamaH, Katoh M.Cancer genetics and genomics of human.FOXfamily genes. Cancer Letters.328:198-206, 2013
  3. MiyabayashiK, Katoh-FukuiY, Ogawa H, Baba T, Shima Y, Sugiyama N,Kitamura K, Morohashi K. Aristaless related homeobox gene, Arx, is implicatedin mouse fetal Leydig cell differentiation possibly through expressing in theprogenitor cells. PLOS ONE. 8:e68050, 2013
  4. Fukami M,Homma K, Hasegawa T, OgataT. Backdoor pathway forDihydrotestosterone Biosynthesis: Implications for normaland abnormal human sex development. Developmental Dynamics. 242(4):320-329