Identification of the germline-derived GNAS gain-of-function mutations and clarification of the novel mechanism leading to GNAS loss-of-function

• Project/Area Number: 17H04204
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: OGATA TSUTOMU 浜松医科大学, 医学部, 教授 (40169173)
• Co-Investigator(Kenkyū-buntansha): 深見 真紀 国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 部長 (40265872)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: GNAS / 抗利尿不適合性腎症候群 / 機能亢進 / 偽性副甲状腺機能低下症 / 機能低下

Outline of Final Research Achievements

GNAS-Gsa mediates signal transductions of multiple G-protein-coupled receptors. It is biallelically expressed in most tissues including the renal collecting duct and is predominantly expressed from the maternal allele in a few tissues such as the renal proximal tubule. We performed whole exome sequencing and identified novel p.F68_G70del and p.M255V variants in two families with dominantly inherited nephrogenic syndrome of inappropriate antidiuresis (NSIAD). We further performed protein structural analysis, in vitro functional analysis, and model mouse analysis, successfully demonstrating that both variants have gain-of-functions. This study demonstrates for the first time the presence of germline-derived GOF variants of GNAS-Gsa and establishes a novel Gsα-mediated genetic disease. We also identified for the first time that elongation of the GNAS region and insertion of retrotransposon can lead to pseudohypoparathyroidism type Ib.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、第1に世界で初めて生殖細胞由来GNAS-Gsa軽度機能亢進変異の存在を証明し、新規遺伝性疾患を樹立したことにある。さらに、この機能亢進にたいしてAVPR2が最も感受性であること、この変異が体細胞由来高度機能変異で生じるMcCune-Albright症候群を発症しないことも明らかとなった。また、常染色体優性の偽性副甲状腺機能低下症は、STX16欠失を伴うA/B-DMRの低メチル化で生じることが知られていたが、本研究で初めてGNAS領域のゲノム伸展やSVA 型レトロトランスポゾン挿入によっても発症することが示された。これらの成果は、GNAS-Gsaの研究を促進させるものである。

Research Products

• [Journal Article] IGF2 Mutations (2020)
  • Author(s): Masunaga Yohei、Inoue Takanobu、Yamoto Kaori、Fujisawa Yasuko、Sato Yasuhiro、Kawashima-Sonoyama Yuki、Morisada Naoya、Iijima Kazumoto、Ohata Yasuhisa、Namba Noriyuki、Suzumura Hiroshi、Kuribayashi Ryota、Yamaguchi Yu、Yoshihashi Hiroshi、Fukami Maki、Saitsu Hirotomo、Kagami Masayo、Ogata Tsutomu
  • Journal Title: J Clin Endocrinol Metab Volume: 105 Pages: 1-10
  • DOI: 10.1210/clinem/dgz034
  • Peer Reviewed / Open Access
• [Journal Article] De novo ZBTB7A variant in a patient with macrocephaly, intellectual disability, and sleep apnea: implications for the phenotypic development in 19p13.3 microdeletions (2020)
  • Author(s): Ohishi Akira、Masunaga Yohei、Iijima Shigeo、Yamoto Kaori、Kato Fumiko、Fukami Maki、Saitsu Hirotomo、Ogata Tsutomu
  • Journal Title: J Hum Genet Volume: 65 Pages: 181-186
  • DOI: 10.1038/s10038-019-0690-5
  • Peer Reviewed
• [Journal Article] Erythrokeratodermia variabilis et progressiva with a rare GJB3 mutation. (2020)
  • Author(s): Imura K, Ikeya S, Ogata T, Tokura Y
  • Journal Title: J Dermatol Volume: 47
  • DOI: 10.1111/1346-8138.15206
  • 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 Dev Volume: 42 Pages: 363-368
  • DOI: 10.1016/j.braindev.2019.12.012
  • Peer Reviewed
• [Journal Article] A de novo TOP2B variant associated with global developmental delay and autism spectrum disorder. (2020)
  • Author(s): Hiraide T, Watanabe S, Matsybayashi T, Yanagi K, Nakashima M, Ogata T, Saitsu H*
  • Journal Title: Mol Genet Genomic Med Volume: 8
  • DOI: 10.1002/mgg3.11
  • Peer Reviewed / Open Access
• [Journal Article] (Epi)genetic defects of MKRN3 are rare in Asian patients with central precocious puberty. (2019)
  • Author(s): Suzuki E, Shima H, Kagami M, Soneda S, Tanaka T, Yatsuga S, Nishioka J, Oto Y, Kamiya T, Naiki Y, Ogata T, Fujisawa Y, Nakamura A, Kawashima S, Morikawa S, Horikawa R, Sano S, Fukami M
  • Journal Title: Hum Genome Var Volume: - Pages: 7-7
  • DOI: 10.1038/s41439-019-0039-9
  • Peer Reviewed / Open Access
• [Journal Article] Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures (2019)
  • Author(s): Nakashima Mitsuko、Tohyama Jun、Nakagawa Eiji、Watanabe Yoshihiro、Siew Ch’ng Gaik、Kwong Chieng Siik、Yamoto Kaori、Hiraide Takuya、Fukuda Tokiko、Kaname Tadashi、Nakabayashi Kazuhiko、Hata Kenichiro、Ogata Tsutomu、Saitsu Hirotomo、Matsumoto Naomichi
  • Journal Title: J Hum Genet Volume: 64 Pages: 313-322
  • DOI: 10.1038/s10038-018-0559-z
  • Peer Reviewed
• [Journal Article] Coexistence of a CAV3 mutation and a DMD deletion in a family with complex muscular diseases. (2019)
  • Author(s): Hiraide T, Ogata T, Watanabe S, Nakashima M, Fukuda T, Saitsu H*
  • Journal Title: Brain Dev Volume: 41 Pages: 474-479
  • DOI: 10.1016/j.braindev.2019.01.005
  • Peer Reviewed
• [Journal Article] Association of four imprinting disorders and ART (2019)
  • Author(s): Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
  • Journal Title: Clinical Epigenetics Volume: 11 Pages: 21-21
  • DOI: 10.1186/s13148-019-0623-3
  • Peer Reviewed / Open Access
• [Journal Article] Germline-Derived Gain-of-Function Variants of Gsα-Coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate Antidiuresis (2019)
  • Author(s): Miyado Mami、Fukami Maki、Takada Shuji、Terao Miho、Nakabayashi Kazuhiko、Hata Kenichiro、Matsubara Yoichi、Tanaka Yoko、Sasaki Goro、Nagasaki Keisuke、Shiina Masaaki、Ogata Kazuhiro、Masunaga Youhei、Saitsu Hirotomo、Ogata Tsutomu
  • Journal Title: J Am Soc Nephrol Volume: 30 Pages: 877-889
  • DOI: 10.1681/asn.2018121268
  • Peer Reviewed / Open Access
• [Journal Article] Exploring the unique function of imprinting control centers in the PWS/AS-responsible region: finding from array-based methylation analysis in cases with variously sized microdeletions. (2019)
  • Author(s): Matsubara K, Itoh M, Shimizu K, Saito S, Enomoto K, Nakabayashi K, Hata K, Kurosawa K, Ogata T, Fukami M, Kagami M.
  • Journal Title: Clinical Epigenetics Volume: 11 Pages: 36-36
  • DOI: 10.1186/s13148-019-0633-1
  • Peer Reviewed / Open Access
• [Journal Article] Temple Syndrome in a Patient With Variably Methylated CpGs at the Primary MEG3/DLK1:IG-DMR and Severely Hypomethylated CpGs at the Secondary MEG3:TSS-DMR (2019)
  • Author(s): Kagami M, Yanagisawa A, Ota M, Matsuoka K, Nakamura A, Matsubara K, Nakabayashi K, Takada S, Fukami M, Ogata T.
  • Journal Title: Clin Epigenetics Volume: 11 Pages: 41-41
  • DOI: 10.1186/s13148-019-0640-2
  • Peer Reviewed / Open Access
• [Journal Article] MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration (2019)
  • Author(s): Hamanaka K、Takata A、Uchiyama Y、Miyatake S、Miyake N、Mitsuhashi S、Iwama K、Fujita A、Imagawa E、Alkanaq AN、Koshimizu E、Azuma Y、Nakashima M、Mizuguchi T、Saitsu H、Wada Y、Minami S、Katoh-Fukui Y、Masunaga Y、Fukami M、Hasegawa T、Ogata T、Matsumoto N
  • Journal Title: Hum Mol Genet Volume: 印刷中 Pages: 2319-2329
  • DOI: 10.1093/hmg/ddz066
  • Peer Reviewed
• [Journal Article] Unbalanced Y;7 Translocation between Two Low-Similarity Sequences Leading to <b><i>SRY</i></b>-Positive 45,X Testicular Disorders of Sex Development (2019)
  • Author(s): Uehara Erika、Hattori Atsushi、Shima Hirohito、Ishiguro Akira、Abe Yu、Ogata Tsutomu、Ogawa Eishin、Fukami Maki
  • Journal Title: Cytogenet Genome Res Volume: 158 Pages: 115-120
  • DOI: 10.1159/000501378
  • Peer Reviewed
• [Journal Article] KLF11 variant in a family clinically diagnosed with early childhood‐onset type 1B diabetes (2019)
  • Author(s): Ushijima Kikumi、Narumi Satoshi、Ogata Tsutomu、Yokota Ichiro、Sugihara Shigetaka、Kaname Tadashi、Horikawa Yukio、Matsubara Yoichi、Fukami Maki、Kawamura Tomoyuki、The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes
  • Journal Title: Pediatr Diabetes Volume: 20 Pages: 712-719
  • DOI: 10.1111/pedi.12868
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aneuploid rescue precedes X-chromosome inactivation and increases the incidence of its skewness by reducing the size of the embryonic progenitor cell pool. (2019)
  • Author(s): Yoshida T, Miyado M, Mikami M, Suzuki E, Kinjo K, Matsubara K, Ogata T, Akutsu H, Kagami M and Fukami M.
  • Journal Title: Hum Reprod Volume: 34 Pages: 1762-1769
  • DOI: 10.1093/humrep/dez117
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive clinical and molecular studies in split-hand/foot malformation: identification of two plausible candidate genes (LRP6 and UBA2) (2019)
  • Author(s): Yamoto Kaori、Saitsu Hirotomo、Nishimura Gen、Kosaki Rika、Takayama Shinichiro、Haga Nobuhiko、Tonoki Hidefumi、Okumura Akihisa、Horii Emiko、Okamoto Nobuhiko、Suzumura Hiroshi、Ikegawa Shiro、Kato Fumiko、Fujisawa Yasuko、Nagata Eiko、Takada Shuji、Fukami Maki、Ogata Tsutomu
  • Journal Title: Eur J Hum Gene Volume: 27 Pages: 1845-1857
  • DOI: 10.1038/s41431-019-0473-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] De novo AFF3 variant in a patient with mesomelic dysplasia with foot malformation (2019)
  • Author(s): Shimizu Daisuke、Sakamoto Rieko、Yamoto Kaori、Saitsu Hirotomo、Fukami Maki、Nishimura Gen、Ogata Tsutomu
  • Journal Title: J Hum Genet Volume: 64 Pages: 1041-1044
  • DOI: 10.1038/s10038-019-0650-0
  • Peer Reviewed
• [Journal Article] Gain-of-function mutations in G-protein coupled receptor genes associated with human endocrine disorders. (2018)
  • Author(s): Fukami M, Suzuki E, Igarashi M, Miyado M and Ogata T.
  • Journal Title: Clin Endocrinol Volume: 88 Pages: 351-359
  • DOI: 10.1111/cen.13496
  • Peer Reviewed / Open Access
• [Journal Article] A de novo 50-bp <b><i>GNAS</i></b> Intragenic Duplication in a Patient with Pseudohypoparathyroidism Type 1a (2018)
  • Author(s): Suzuki Erina、Bo Ryosuke、Sue Kaori、Awano Hiroyuki、Ogata Tsutomu、Narumi Satoshi、Kagami Masayo、Sano Shinichiro、Fukami Maki
  • Journal Title: Cytogenet Genome Res Volume: 153 Pages: 125-130
  • DOI: 10.1159/000485644
  • Peer Reviewed
• [Journal Article] Partial androgen insensitivity syndrome caused by a deep intronic mutation creating an alternative splice acceptor site of the AR gene (2018)
  • Author(s): Ono Hiroyuki、Saitsu Hirotomo、Horikawa Reiko、Nakashima Shinichi、Ohkubo Yumiko、Yanagi Kumiko、Nakabayashi Kazuhiko、Fukami Maki、Fujisawa Yasuko、Ogata Tsutomu
  • Journal Title: Sci Rep Volume: 8 Pages: 177-184
  • DOI: 10.1038/s41598-018-20691-9
  • Peer Reviewed / Open Access
• [Journal Article] GATA4 mutations are uncommon in patients with 46,XY disorders of sex development without heart anomaly. (2018)
  • Author(s): Igarashi M, Mizuno K, Kon M, Narumi S, Kojima Y, Hayashi Y, Ogata T, Fukami M*
  • Journal Title: Asian J Androl Volume: 20 Pages: 629-631
  • Peer Reviewed
• [Journal Article] GATA4 variant identified by whole exome sequencing in a Japanese family with atrial septal defect: implications for male sex development. (2018)
  • Author(s): Shimizu D, Iwashima S, Sato K, Hayano S, Fukami M, Saitsu H, Ogata T
  • Journal Title: Clin Case Rep Volume: 6 Pages: 2229-2233
  • DOI: 10.1002/ccr3.1851
  • Peer Reviewed / Open Access
• [Journal Article] Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology (2018)
  • Author(s): Inoue Takanobu、Yagasaki Hideaki、Nishioka Junko、Nakamura Akie、Matsubara Keiko、Narumi Satoshi、Nakabayashi Kazuhiko、Yamazawa Kazuki、Fuke Tomoko、Oka Akira、Ogata Tsutomu、Fukami Maki、Kagami Masayo
  • Journal Title: J Med Genet Volume: 印刷中
  • DOI: 10.1136/jmedgenet-2018-105463
  • Peer Reviewed
• [Journal Article] 11-oxygenated C19 steroids as circulating androgens in women with polycystic ovary syndrome (2018)
  • Author(s): Yoshida T, Matsuzaki T, Miyado M, Saito K, Iwasa T, Matsubara Y, Ogata T, Irahara M, Fukami M.
  • Journal Title: Endocr J Volume: 65 Issue: 10 Pages: 979-990
  • DOI: 10.1507/endocrj.ej18-0212 10.1507/endocrj.EJ18-0212
  • NAID: 130007501323
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Congenital limb deficiency in Japan: a cross-sectional nationwide survey on its epidemiology (2018)
  • Author(s): Mano Hiroshi、Fujiwara Sayaka、Takamura Kazuyuki、Kitoh Hiroshi、Takayama Shinichiro、Ogata Tsutomu、Hashimoto Shuji、Haga Nobuhiko
  • Journal Title: BMC Musculoskelet Disord Volume: 19 Pages: 262-262
  • DOI: 10.1186/s12891-018-2195-3
  • Peer Reviewed / Open Access
• [Journal Article] Clinical characteristics of a Japanese patient with Bardet-Biedl syndrome caused by BBS10 mutations (2018)
  • Author(s): Kurata Kentaro、Hosono Katsuhiro、Hikoya Akiko、Kato Akihiko、Saitsu Hirotomo、Minoshima Shinsei、Ogata Tsutomu、Hotta Yoshihiro
  • Journal Title: Jpn J Ophthalmol A Volume: 62 Pages: 458-466
  • DOI: 10.1007/s10384-018-0591-8
  • Peer Reviewed
• [Journal Article] Characterization of parent-of-origin methylation using the Illumina Infinium MethylationEPIC array platform (2018)
  • Author(s): Hernandez Mora Jose R、Tayama Chiharu、S?nchez-Delgado Marta、Monteagudo-S?nchez Ana、Hata Kenichiro、Ogata Tsutomu、Medrano Jose、Poo-Llanillo Maria E、Sim?n Carlos、Moran Sebastian、Esteller Manel、Tenorio Jair、Lapunzina Pablo、Kagami Masayo、Monk David、Nakabayashi Kazuhiko
  • Journal Title: Epigenomics Volume: 10 Pages: 941-954
  • DOI: 10.2217/epi-2017-0172
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maternal Uniparental Disomy for Chromosome 20: Physical and Endocrinological Characteristics of Five Patients (2018)
  • Author(s): Kawashima Sayaka、Nakamura Akie、Inoue Takanobu、Matsubara Keiko、Horikawa Reiko、Wakui Keiko、Takano Kyoko、Fukushima Yoshimitsu、Tatematsu Toshi、Mizuno Seiji、Tsubaki Junko、Kure Shigeo、Matsubara Yoichi、Ogata Tsutomu、Fukami Maki、Kagami Masayo
  • Journal Title: J Clin Endocrinol Metab Volume: 103 Pages: 2083-2088
  • DOI: 10.1210/jc.2017-02780
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] STX2 is a causative gene for nonobstructive azoospermia. (2018)
  • Author(s): Nakamura S, Kobori Y, Ueda Y, Tanaka Y, Ishikawa H, Yoshida A, Katsumi M, Saito K, Nakamura A, Ogata T, Okada H, Nakai H, Miyado M and Fukami M.
  • Journal Title: Hum Mutat Volume: 印刷中 Pages: 0-0
  • DOI: 10.1002/humu.23423
  • Peer Reviewed
• [Journal Article] A case of paternal uniparental isodisomy for chromosome 7 associated with overgrowth (2018)
  • Author(s): Nakamura Akie、Muroya Koji、Ogata-Kawata Hiroko、Nakabayashi Kazuhiko、Matsubara Keiko、Ogata Tsutomu、Kurosawa Kenji、Fukami Maki、Kagami Masayo
  • Journal Title: Journal of Medical Genetics Volume: 55 Pages: 2017-104986
  • DOI: 10.1136/jmedgenet-2017-104986
  • Peer Reviewed
• [Journal Article] Functional missense and splicing variants in the retinoic acid catabolizing enzyme CYP26C1 in idiopathic short stature. (2018)
  • Author(s): Montalbano A, Juergensen L, Fukami M, Thiel, CT, Hauer NH, Roeth R, Weiss B, Naiki Y, Ogata T, Hassel D, Rappold GA*
  • Journal Title: Eur J Hum Genet Volume: 26 Pages: 1113-1120
  • DOI: 10.1038/s41431-018-0148-9
  • Peer Reviewed
• [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: Hum Genet Volume: 137 Pages: 95-104
  • DOI: 10.1007/s00439-017-1863-y
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal Serum and Urine Steroid Metabolite Profiling in a 46,XY Infant with Prenatally Identified POR Deficiency. (2018)
  • Author(s): Ono H, Numakura C, Homma K, Hasegwa T, Tsutsumi S, Kato F, Fujisawa Y, Fukami M, Ogata T*
  • Journal Title: Steroid Biochem Mol Biol Volume: 178 Pages: 177-184
  • Peer Reviewed
• [Journal Article] Protein-altering variants of PTPN2 in childhood-onset Type 1A diabetes (2018)
  • Author(s): Okuno M.、Ayabe T.、Yokota I.、Musha I.、Shiga K.、Kikuchi T.、Kikuchi N.、Ohtake A.、Nakamura A.、Nakabayashi K.、Okamura K.、Momozawa Y.、Kubo M.、Suzuki J.、Urakami T.、Kawamura T.、Amemiya S.、Ogata T.、Sugihara S.、Fukami M.、the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes
  • Journal Title: Diabet Med Volume: 35 Pages: 376-380
  • DOI: 10.1111/dme.13566
  • Peer Reviewed
• [Journal Article] Two patients with MIRAGE syndrome lacking haematological features: role of somatic second-site reversion SAMD9 mutations. (2018)
  • Author(s): Shima H, MD*, Koehler K*, Nomura Y, Sugimoto K, Satoh A, Ogata T, Fukami M, Schuelke M, Huebner A, Narum S
  • Journal Title: J Med Genet Volume: 55 Pages: 81-85
  • DOI: 10.1136/jmedgenet-2017-105020
  • Peer Reviewed
• [Journal Article] FGFR1 disruption identified by whole genome sequencing in a male with a complex chromosomal rearrangement and hypogonadotropic hypogonadism (2018)
  • Author(s): Yamoto Kaori、Okamoto Shingo、Fujisawa Yasuko、Fukami Maki、Saitsu Hirotomo、Ogata Tsutomu
  • Journal Title: Am J Med Genet A Volume: 176 Pages: 139-143
  • DOI: 10.1002/ajmg.a.38535
  • Peer Reviewed
• [Journal Article] Expression of xenobiotic biomarkers CYP1 family in preputial tissue of patients with hypospadias and phimosis and its association with DNA methylation level of SRD5A2 minimal promoter. (2018)
  • Author(s): Ohsako S, Aiba T, Miyado M, Fukami M, Ogata T, Hayashi Y, Mizuno K and Kojima Y.
  • Journal Title: Arch Environ Contam Toxicol Volume: 74 Pages: 240-247
  • DOI: 10.1007/s00244-017-0466-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive screening for monogenic diabetes in 89 Japanese children with insulin-requiring antibody-negative type 1 diabetes (2018)
  • Author(s): Ushijima K, Fukami M, Ayabe T, Narumi S, Okuno M, Nakamura A, Takahashi T, Ihara K, Ohkubo K, Tachikawa E, Nakayama S, Arai J, Kikuchi N, Kikuchi T, Kawamura T, Urakami T, Hata K, Nakabayashi K, Matsubara Y, Amemiya S, Ogata T, Yokota I, Sugihara S
  • Journal Title: Pediatr Diabetes Volume: 19 Pages: 243-250
  • DOI: 10.1111/pedi.12544
  • Peer Reviewed
• [Journal Article] Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients (2017)
  • Author(s): Kagami Masayo、Nagasaki Keisuke、Kosaki Rika、Horikawa Reiko、Naiki Yasuhiro、Saitoh Shinji、Tajima Toshihiro、Yorifuji Tohru、Numakura Chikahiko、Mizuno Seiji、Nakamura Akie、Matsubara Keiko、Fukami Maki、Ogata Tsutomu
  • Journal Title: Genet Med. Volume: 19 Pages: 1356-1366
  • DOI: 10.1038/gim.2017.53
  • Peer Reviewed / Open Access
• [Journal Article] Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects. (2017)
  • Author(s): Inoue T, Nakamura A, Fuke T, Yamazawa K, Sano S, Matsubara K, Mizuno S, Matsukura Y, Harashima C, Hasegawa T, Nakajima H, Tsumura K, Kizaki Z, Oka A, Ogata T, Fukami M, Kagami M.
  • Journal Title: Clin Epigenetics. Volume: 9 Pages: 52-52
  • DOI: 10.1186/s13148-017-0350-6
  • Peer Reviewed / Open Access
• [Journal Article] De novo IGF2 mutation on the paternal allele in a patient with Silver-Russell syndrome and ectrodactyly (2017)
  • Author(s): Yamoto Kaori、Saitsu Hirotomo、Nakagawa Norio、Nakajima Hisakazu、Hasegawa Tatsuji、Fujisawa Yasuko、Kagami Masayo、Fukami Maki、Ogata Tsutomu
  • Journal Title: Hum Mutat. Volume: 38 Pages: 953-958
  • DOI: 10.1002/humu.23253
  • Peer Reviewed
• [Journal Article] Mosaic upd(14)pat in a patient with mild features of Kagami-Ogata syndrome (2017)
  • Author(s): Haug Marte G.、Brendehaug Atle、Houge Gunnar、Kagami Masayo、Ogata Tsutomu
  • Journal Title: Clin Case Rep. Volume: 6 Pages: 91-95
  • DOI: 10.1002/ccr3.1300
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] (Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I (2017)
  • Author(s): Sano Shinichiro、Nakamura Akie、Matsubara Keiko、Nagasaki Keisuke、Fukami Maki、Kagami Masayo、Ogata Tsutomu
  • Journal Title: J Endocr Soc. Volume: 2 Pages: 9-23
  • DOI: 10.1210/js.2017-00293
  • Peer Reviewed / Open Access
• [Journal Article] Diagnosis and management of Silver?Russell syndrome: first international consensus statement (2017)
  • Author(s): Wakeling Emma L、Brioude Frdric、Lokulo-Sodipe Oluwakemi、O'Connell Susan M.、Salem Jennifer、Bliek Jet、Canton Ana P. M.、Chrzanowska Krystyna H.、Davies Justin H.、Dias Renuka P.、Tsutomu Ogata
  • Journal Title: Nat Rev Endocrinol. Volume: 13 Pages: 105-124
  • DOI: 10.1038/nrendo.2016.138
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 世界初の生殖細胞由来GNAS機能亢進型バリアントの同定 (2020)
  • Author(s): 宮戸真美，深見真紀，緒方勤
  • Organizer: 第30回バゾプレシン研究会
• [Presentation] Germline-derived Gain-of-Function Variants of Gsα-coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate Antidiuresis: The First report (2019)
  • Author(s): Fukami M, Miyado M, Takada S, Sasaki G, K Nagasaki, Masunaga M, Saitsu H, Ogata T
  • Organizer: The 58th Annual Meeting of European Pediatric Endocrinology
  • Int'l Joint Research
• [Presentation] Germline-derived gain-of-function variants of Gsα-coding GNAS gene identified in nephrogenic syndrome of inappropriate antidiuresis: the first report (2019)
  • Author(s): Miyado M, Fukami M, Matsubara Y, Tanaka Y, Sasaki G, Nagasaki K, Masunaga Y, Saitsu H and Ogata T.
  • Organizer: 第53回日本小児内分泌学会学術集会
• [Presentation] IGF2: a paternally expressed gene essential for pre- and post-natal growth and placental development. In: Symposium Novel gene discoveries in Mendelian diseases. (2018)
  • Author(s): Ogata T
  • Organizer: 2018 International Joint Conference on Genetics & Medicine (Genetic Society of Korea, Korean Society of Medical Genetics & Genomics, and East-Asian Union of Human Genetics Society).
  • Int'l Joint Research / Invited
• [Presentation] Kagami-Ogata症候群：発症機序解明と臨床診断基準・遺伝学的診断法の確立 (2018)
  • Author(s): 緒方勤
  • Organizer: 日本人類遺伝学会第63回大会
  • Invited
• [Presentation] ARTとインプリンティング疾患発症の関連について (2018)
  • Author(s): 緒方勤
  • Organizer: 第63回日本生殖医学会学術講演会・総会
  • Invited
• [Presentation] 性スペクトラム (2018)
  • Author(s): 緒方勤
  • Organizer: 第28回日本内分泌学会臨床内分泌代謝アップデート
  • Invited
• [Presentation] 小児の遺伝性間脳下垂体疾患 (2018)
  • Author(s): 緒方勤
  • Organizer: 第28回日本間脳下垂体腫瘍学会
  • Invited
• [Presentation] 20番染色体母性片親性ダイソミー 5 例の臨床像の検討 (2018)
  • Author(s): 川嶋 明香、中村 明枝、井上 毅信、堀川 玲子、涌井 敬子、髙野 享子、水野 誠司、椿 淳子、緒方 勤、深見 真紀、鏡 雅代
  • Organizer: 第40回日本小児遺伝学会学術集会
• [Presentation] PHP-I 型の 69 例における（エピ）遺伝子型－表現型解析 (2018)
  • Author(s): 佐野伸一朗，中村 明枝，松原 圭子，加藤 芙弥子，深見 真紀，鏡 雅代，緒方 勤
  • Organizer: 第40回日本小児遺伝学会学術集会
• [Presentation] Temple症候群32症例における遺伝子診断に基づいた臨床像の検討 (2017)
  • Author(s): 鏡 雅代、長崎啓祐、小崎里華、齋藤伸治、中村明枝、松原圭子、深見真紀、緒方 勤
  • Organizer: 第120回日本小児科学会学術集会
• [Presentation] 偽性副甲状腺機能低下症の（epi）genotype-phenotype correlation (2017)
  • Author(s): 佐野 伸一朗、中村 明枝、松原 圭子、長崎 啓介、深見 真紀、緒方 勤、鏡 雅代
  • Organizer: 第90回日本内分泌学会学術総会
• [Presentation] ヒトの成長と成熟：Auxologyとインプリンティングの観点から (2017)
  • Author(s): 緒方 勤
  • Organizer: 第90回日本内分泌学会学術総会
• [Presentation] Beckwith-Wiedemann syndromeとPHP-Ibの臨床像を呈したMultilocus imprinting disturbanceの女児例 (2017)
  • Author(s): 佐野 伸一朗、長崎 啓介、松原 圭子、中村 明枝、深見 真紀、緒方 勤
  • Organizer: 第90回日本内分泌学会学術総会
• [Presentation] DE NOVO IGF2 MUTATION ON THE PATERNAL ALLELE IN A PATIENT WITH SILVER-RUSSELL SYNDROME AND ECTRODACTYLY (2017)
  • Author(s): Kaori Yamoto, Hirotomo Saitsu, Norio Nakagawa, Hisakazu Nakajima, Tatsuji Hasegawa, Yasuko Fujisawa, Masayo Kagami, Maki Fukami, Tsutomu Ogata
  • Organizer: The 10th International Meeting of Pediatric Endocrinology
• [Presentation] 患者生体試料を用いた14q32.2インプリンティング領域のメチローム・トランスクリプトーム解析 (2017)
  • Author(s): 鏡 雅代、松原 圭子、早野 崇英、細道 一善、高田 修治、井ノ上 逸朗、緒方 勤、深見 真紀
  • Organizer: 第51回日本小児内分泌学会学術集会
• [Presentation] 20番染色体母性片親性ダイソミー5例の臨床像の検討 (2017)
  • Author(s): 川嶋 明香、中村 明枝、井上 毅信、堀川 玲子、高野 亨子、水野 誠司、椿 淳子、緒方 勤、深見 真紀、鏡 雅代
  • Organizer: 第51回日本小児内分泌学会学術集会
• [Presentation] IGF2遺伝子のdenovo変異が父親由来アレルで同定された裂手症合併Silver-Russell症候群の1例 (2017)
  • Author(s): 矢本 香織、才津 浩智、中川 憲夫、中島 久和、長谷川 龍志、藤澤 泰子、鏡 雅代、深見 真紀、緒方 勤
  • Organizer: 第51回日本小児内分泌学会学術集会
• [Presentation] PHP-I型の69例における（エピ）遺伝子型－表現型解析 (2017)
  • Author(s): 佐野 伸一朗、中村 明枝、松原 圭子、加藤 芙弥子、深見 真紀、鏡 雅代、緒方 勤
  • Organizer: 第51回日本小児内分泌学会学術集会
• [Presentation] 6番染色体父性ダイソミーによる6q24関連糖尿病の2症例 (2017)
  • Author(s): 大高 幸之助、中島 信一、加藤 芙弥子、山口 理恵、増永 陽平、小野 裕之、永田 絵子、藤澤 泰子、依藤 亨、緒方 勤
  • Organizer: 第51回日本小児内分泌学会学術集会
• [Presentation] Silver-Russell症候群とTemple症候群における臨床および遺伝学的診断の進歩 (2017)
  • Author(s): 緒方 勤
  • Organizer: 日本人類遺伝学会 第62回大会