Genetic and genomic analysis on the patients with multiple congenital anomalies

• Project/Area Number: 26461538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanagawa Children's Medical Center (Clinical Research Institute)
• Principal Investigator: Kurosawa Kenji 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 部門長 (20277031)
• Research Collaborator: NARUTO Takuya 徳島大学, 大学院医歯薬学研究部人類遺伝学, 助教 (60438124) ; TSURUSAKI Yoshinori 地方独立行政法人神奈川県立病院機構, 神奈川県立こども医療センター・臨床研究所, 主任研究員 (70392040) ; ENOMOTO Yumi 地方独立行政法人神奈川県立病院機構, 神奈川県立こども医療センター・臨床研究所, 研究員 (20506290)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 多発奇形 / 精神遅滞 / 次世代シーケンス / エクソーム解析 / マイクロアレイ / ゲノム支援 / copy number variant / エクソーム / 次世代シーケンサー

Outline of Final Research Achievements

Uncovering the molecular mechanism for birth defects is critical to understand the biological mechanism of human development. To elucidate the causative gene responsible for multiple congenital anomalies of unknown origin, we performed whole exome sequence on the patients with the disorders. This work was supported by MEXT KAKENHI (No.221S0002). 31 patients were enrolled after first screening with standard karyotyping and cytogenetic microarray. Of 31 patients, the causative genomic variants for the disorders could be identified in 9 families (30%). Further analysis will be required to identify the molecular mechanism for these congenital anomalies.

Research Products

• [Journal Article] A case of MECP2 duplication syndrome with gonadotropin-dependent precocious puberty. (2017)
  • Author(s): Tsuji-Hosokawa A, Matsuda N, Kurosawa K, Kashimada K, Morio T.
  • Journal Title: Horm Res Paediatr Volume: 87 Issue: 4 Pages: 271-276
  • DOI: 10.1159/000449222
  • Peer Reviewed
• [Journal Article] A contiguous gene deletion neighboring TWIST1 identified in a patient with Saethre-Chotzen syndrome associated with neurodevelopmental delay: possible contribution of HDAC9. (2017)
  • Author(s): Shimbo H, Oyoshi T, Kurosawa K.
  • Journal Title: Congenit Anom (Kyoto) Volume: 印刷中 Issue: 1 Pages: 33-35
  • DOI: 10.1111/cga.12216
  • Peer Reviewed
• [Journal Article] A novel UBE2A mutation causes X-linked intellectual disability type Nascimento. (2017)
  • Author(s): Tsurusaki Y, Ohashi I, Enomoto Y, Naruto T, Mitsui J, Kurosawa K, Aida N
  • Journal Title: Human Genome Variation Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations. (2016)
  • Author(s): Yaoita M, Niihori T, Mizuno S, Okamoto N, Hayashi S, Watanabe A, Yokozawa M, Suzumura H, Nakahara A, Nakano Y, Hokosaki T, Ohmori A, Sawada H, Migita O, Mima A, Lapunzina P, Santos-Simarro F, García-Miñaúr S, Ogata T, Kawame H, Kurosawa K, Ohashi H, Inoue S, Matsubara Y, Kure S, Aoki Y.
  • Journal Title: Hum Genet. Volume: 135 Issue: 2 Pages: 209-222
  • DOI: 10.1007/s00439-015-1627-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A postzygotic NRAS mutation in a patient with Schimmelpenning syndrome. (2015)
  • Author(s): Kuroda Y, Ohashi I, Enomoto Y, Naruto T, Baba N, Tanaka Y, Aida N, Okamoto N, Niihori T, Aoki Y, Kurosawa K.
  • Journal Title: Am J Med Genet A. Volume: 167A Issue: 9 Pages: 2223-2225
  • DOI: 10.1002/ajmg.a.37135
  • Peer Reviewed
• [Journal Article] Delineation of the KIAA2022 mutation phenotype: Two patients with X-linked intellectual disability and distinctive features. (2015)
  • Author(s): Kuroda Y, Ohashi I, Naruto T, Ida K, Enomoto Y, Saito T, Nagai J, Wada T, Kurosawa K.
  • Journal Title: Ａｍ Ｊ Ｍｅｄ Ｇｅｎｅｔ Ａ Volume: 167 Issue: 6 Pages: 1349-53
  • DOI: 10.1002/ajmg.a.37002
  • Peer Reviewed
• [Journal Article] West Syndrome in a Patient With Schinzel-Giedion Syndrome. (2015)
  • Author(s): Miyake F, Kuroda Y, Naruto T, Ohashi I, Takano K, Kurosawa K.
  • Journal Title: J Child Neurol Volume: 30 Issue: 7 Pages: 932-6
  • DOI: 10.1177/0883073814541468
  • Peer Reviewed
• [Journal Article] Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome) (2015)
  • Author(s): Kagami M, Kurosawa K, Miyazaki O, Ishino F, Matsuoka K, Ogata T
  • Journal Title: Eur J Hum Genet Volume: 2 Issue: 11 Pages: 1-8
  • DOI: 10.1038/ejhg.2015.13
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Microdeletion of 19p13.3 in a girl with Peutz-Jeghers syndrome, intellectual disability, hypotonia, and distinctive features. (2015)
  • Author(s): Kuroda Y, Saito T, Nagai J, Ida K, Naruto T, Masuno M, Kurosawa K
  • Journal Title: Am J Med Genet A Volume: 167A Issue: 2 Pages: 389-393
  • DOI: 10.1002/ajmg.a.36813
  • Peer Reviewed
• [Journal Article] Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2. (2015)
  • Author(s): Kuroda Y, Ohashi I, Saito T, Nagai JI, Ida K, Naruto T, Wada T, Kurosawa K
  • Journal Title: Am J Med Genet A Volume: 167A Issue: 11 Pages: 2873-2878
  • DOI: 10.1002/ajmg.a.36704
  • Peer Reviewed
• [Presentation] 次世代シーケンサーにより診断されたKBG症候群の臨床像 (2016)
  • Author(s): 横井貴之、湊川真理、羽田野ちひろ、榎本友美、鶴崎美徳、成戸卓也、小崎健次郎、黒澤健司
  • Organizer: 第39回日本小児遺伝学会
  • Place of Presentation: 慶應義塾大学（東京都港区）
  • Year and Date: 2016-12-09
• [Presentation] Dosage Changes of NIPBL cause various types of neurodevelopmental disability. (2016)
  • Author(s): Hatano C, Yokoi T, Enomoto Y, Tsurusaki Y, Saito T, Nagai J, Kurosawa K
  • Organizer: he 13th International Congress of Human Genetics
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Structural brain abnormalities associated with deletion at chromosome 2p16.1. (2016)
  • Author(s): Shimbo H, Yokoi T, Mizuno S, Suzumura H, Aida N, Nagai J, Ida K, Enomoto Y, Hatano C, Kurosawa K.
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Early development of rare tumors in individuals with congenital malformation syndrome. (2016)
  • Author(s): Minatogawa M, Iwasaki F, Fukuda K, Hatano C, Yokoi T, Enomoto Y, Ida K, Tsurusaki Y, Harada N, Saitou T, Nagai J, Goto H, Kurosawa K
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Next-generation sequencing identifies novel ARID1B mutations in patients with Coffin-Siris syndrome. (2016)
  • Author(s): Tsurusaki Y, Enomoto Y, Yokoi T, Hatano C, Ida K, Kurosawa K
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] 次世代シーケンサー(NGS)を用いて診断したKBG症候群の2例 (2016)
  • Author(s): 中村航、羽田野ちひろ、横井貴之、黒澤健司、榎本友美、鶴崎美徳、原田法彰、永井淳一
  • Organizer: 第339回日本小児科学会神奈川県地方会
  • Place of Presentation: 神奈川県総合医療会館（神奈川県横浜市中区）
  • Year and Date: 2016-03-12
• [Presentation] 原因不明遺伝子関連疾患におけるゲノム解析の実際 (2015)
  • Author(s): 黒澤健司、羽田野ちひろ、横井貴之
  • Organizer: 第337回日本小児科学会神奈川県地方会
  • Place of Presentation: 神奈川県総合医療会館（神奈川県横浜市中区）
  • Year and Date: 2015-11-28
• [Presentation] EGFRの機能喪失型変異の複合ヘテロ接合を有する一男児例 (2015)
  • Author(s): 横井貴之、羽田野ちひろ、鶴﨑美徳、榎本友美、成戸卓也、林至恩、小林正久、井田博幸、黒澤健司
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-14
• [Presentation] Deletion of KIRREL3 causes intellectual disability in Jacobsen syndrome. (2015)
  • Author(s): Hatano C, Yokoi T, Enomoto Y, Saito T, Nagai J, Kurosawa K.
  • Organizer: 米国人類遺伝学会2015
  • Place of Presentation: ボルチモア（米国）
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] Genetic analysis of autism spectrum disorder(ASD) based on developed diagnostic flows using next-generation sequencing (NGS). (2015)
  • Author(s): Enomoto Y, Yokoi T, Hatano C, Ida K, Naruto T, Kurosawa K.
  • Organizer: 米国人類遺伝学会2015
  • Place of Presentation: ボルチモア（米国）
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] 次世代シーケンサーを用いた遺伝性疾患におけるコピー数異常の検出． (2015)
  • Author(s): 横井貴之、大橋育子、黒田友紀子、羽田野ちひろ、榎本友美、成戸卓也、升野光雄、黒澤健司
  • Organizer: 第39回日本遺伝カウンセリング学会学術集会
  • Place of Presentation: 三井ガーデンホテル千葉（千葉県千葉市中央区）
  • Year and Date: 2015-06-26
• [Presentation] 遺伝性小児神経領域疾患診断への臨床エクソームの導入 (2015)
  • Author(s): 羽田野ちひろ、横井貴之、渡邊肇子、露崎悠、新保裕子、榎本友美、成戸卓也、大橋育子、黒田友紀子、後藤知英、黒澤健司
  • Organizer: 第57回日本小児神経学会学術集会
  • Place of Presentation: 帝国ホテル大阪（大阪府大阪市北区）
  • Year and Date: 2015-05-28
• [Presentation] CASK truncating変異を有する男児はモザイク例のみ生存しうる (2015)
  • Author(s): 羽田野ちひろ、横井貴之、黒田友紀子、大橋育子、安西里恵、井合瑞江、黒澤健司
  • Organizer: 第118回日本小児科学会学術集会
  • Place of Presentation: 大阪国際会議場／リーがロイヤルホテル大阪（大阪府大阪市北区）
  • Year and Date: 2015-04-17
• [Presentation] Rubinstein-Taybi症候群の成人例における脳血管障害 (2015)
  • Author(s): 横井貴之、羽田野ちひろ、伊藤進、相田典子、呉繁夫、升野光雄、黒澤健司
  • Organizer: 第118回日本小児科学会学術集会
  • Place of Presentation: 大阪国際会議場／リーがロイヤルホテル大阪（大阪府大阪市北区）
  • Year and Date: 2015-04-17
• [Presentation] メンデル遺伝病エクソーム解析による多発奇形・発達遅滞（MCA / ID・DD ）の解析 (2014)
  • Author(s): 横井貴之、大橋育子、黒田友紀子、羽田野ちひろ、榎本友美、成戸卓也、升野光雄、井田博幸、黒澤健司
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] 小児病院の診断における次世代シーケンサーの利用 (2014)
  • Author(s): 榎本友美、大橋育子、黒田友紀子、羽田野ちひろ、横井貴之、井田一美、成戸卓也、黒澤健司
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] 小児科診療における次世代シーケンス解析 (2014)
  • Author(s): 黒澤健司
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
  • Invited
• [Presentation] Contiguous deletion of CADPS2 and GRM8 associates with severe autism spectrum disorder. (2014)
  • Author(s): Hatano C, Yokoi T, Wakui K, Enomoto K, Kuroda Y, Ohashi I, Kosaki R, Kurosawa K
  • Organizer: American Society of Human Genetics 64th Annual Meeting
  • Place of Presentation: SanDiego
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] 診療における次世代シーケンス解析‐結果のまとめ方と伝え方‐ (2014)
  • Author(s): 黒澤健司
  • Organizer: 第38回日本遺伝カウンセリング学会
  • Place of Presentation: 東大阪市
  • Year and Date: 2014-06-27 – 2014-06-29
  • Invited
• [Presentation] 6p21.33 microdeletion associated with EHMT2 haploinsufficiency and intellectual disability. (2014)
  • Author(s): Kurosawa K, Ohashi I, Kuroda Y, Naruto T, Saito T. J Nagai.
  • Organizer: European Human Genetics Conference 2014
  • Place of Presentation: Milan
  • Year and Date: 2014-05-31 – 2014-06-02
• [Book] 別冊日本臨床 No.29.神経症候群（第2版）Ⅳ (2014)
  • Author(s): 黒澤健司
  • Publisher: 日本臨床社