The exhaustive analysis for congenital hypothyroidism using the next generation sequencer

• Project/Area Number: 24659495
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: MARUO YOSHIHIRO 滋賀医科大学, 医学部, 講師 (80314160)
• Co-Investigator(Kenkyū-buntansha): MATSUI Katsuyuki 滋賀医科大学, 医学部, 助教 (60595924) ; MORI Asami 滋賀医科大学, 医学部, 非常勤講師 (70437151)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 先天性甲状腺機能低下症 / 次世代シーケンサー / Dual oxidase 2 / DUOX2 / 小児内分泌学

Research Abstract

We detected many novel mutations of the thyroid hormone generating genes including dual oxidase 2 (DUOX2), PAX8 and Pendrin (PDS) and so on by the exhaustive analysis of causative genes of congenital hypothyroidism using the next generation sequencer. Furthermore, We performed family analysis and We considered whether the variation that we discovered was the etiology to congenital hypothyroidism and elucidated the hereditary genetic causes.
We identified nine new mutations about DUOX2 and got knowledge to contribution of DUOX2 mutations to elucidate genetic pahtology. In many patients with congenital hypothyroidism, the causative gene could not been detected. But this study showed that DUOX2 defect is one of the main causes of congenital hypothyroidism. In addition, about other genes, we could identify new mutations and obtained the data which contributed to elucidation of genetic causes.

Research Products

• [Journal Article] Bilirubin Uridine Diphosphate-Glucuronosyltransferase Variation Is a Genetic Basis of Breast Milk Jaundice. (2014)
  • Author(s): Maruo Y, Morioka Y, Fujito H, Nakahara S, Yanagi T, Matsui K, Mori A, Sato H, Tukey RH, Takeuchi Y.
  • Journal Title: J Pediatr Volume: may Issue: 1 Pages: 7-7
  • DOI: 10.1016/j.jpeds.2014.01.060
  • Peer Reviewed
• [Journal Article] Molecular and clinical characterization of glucokinase maturity-onset diabetes of the young (GCK-MODY) in Japanese patients. (2014)
  • Author(s): Kawakita R, Hosokawa Y, Fujimaru R, Tamagawa N, Urakami T, Takasawa K, Moriya K, Mizuno H, Maruo Y, Takuwa M, Nagasaka H, Nishi Y, Yamamoto Y, Aizu K, Yorifuji T.
  • Journal Title: Diabet Med Volume: mar Issue: 11 Pages: 17-17
  • DOI: 10.1111/dme.12487
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus (2013)
  • Author(s): Yorifuji T, Fujimaru R, Hosokawa Y, Tamagawa N, Shiozaki M, Aizu K, Jinno K, Maruo Y, Nagasaka H, Tajima T, Kobayashi K, Urakami T.
  • Journal Title: Pediatr Diabetes Volume: 14(3) Pages: 230-230
  • Peer Reviewed
• [Journal Article] UDP-グルクロン酸転移酵素1型ファミリー共通エクソン変異(p.P364L)の薬物代謝に及ぼす影響 (2012)
  • Author(s): 三村由卯、丸尾良浩、森岡依子、佐藤浩、竹内義博
  • Journal Title: 日本小児臨床薬理学会雑誌 Volume: 25巻 Pages: 129-134
  • Peer Reviewed
• [Journal Article] Compound heterozygote of a novel missense mutation (p.K402T) and a double missense mutation (p.[G71R;Y486D]) in type II Crigler-Najjar syndrome (2011)
  • Author(s): Maruo Y, Ozgenc F, Mimura Y, Ota Y, Matsui K, Takahashi H, Mori A, Taga T, Takano T, Sato H, Takeuchi Y.
  • Journal Title: J Pediatr Gastroenterol Nutr Volume: 52(3) Pages: 362-5
• [Journal Article] Inhibitory effect of 5β-pregnane-3α,20β-diol on transcriptional activity and enzyme activity of human bilirubin UDP-glucuronosyltransferase (2011)
  • Author(s): Ota Y, Maruo Y, Matsui K, Mimura Y, Sato H, Takeuchi Y.
  • Journal Title: Pediatr Res Volume: 70(5) Pages: 453-7
• [Journal Article] Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and varicella zoster virus encephalitis during treatment of medulloblastoma (2011)
  • Author(s): Ohta M, Taga T, Nomura A, Kato H, Takano T, Maruo Y, Takeuchi Y, Ishida M, Ohta S.
  • Journal Title: J Med Virol Volume: 83(9) Pages: 1582-4
• [Journal Article] Effect of common exon variant (p.P364L) on drug glucuronidation by the human UDP-glucuronosyltransferase 1 family (2011)
  • Author(s): Mimura Y, Maruo Y, Ohta Y, Sato H, Takeuchi Y.
  • Journal Title: Basic Clin Pharmacol Toxicol Volume: 109(6) Pages: 486-93
• [Journal Article] Dual oxidase 2(DUOX2)の両アレル変異による一過性甲状腺機能低下症の8例 (2011)
  • Author(s): 丸尾良浩、三村由卯、森岡依子、松井克之、森麻美、佐藤浩、竹内義博
  • Journal Title: ホルモンと臨床 Volume: 59巻 Pages: 1057-1062
• [Journal Article] A novel large deletion (exons 12, 13) and a missense mutation (p.G46R) in the PAH in a Japanese patient with phenylketonuria
  • Author(s): Maruo Y, Suzaki M, Matui K, Mimura Y, Mori A, Shintaku H, Takeuchi Y.
  • Journal Title: World J Pediatr Volume: (in press)
• [Presentation] Dual oxidase 2 (DUOX2)異常症の臨床像の解明23例の解析より (2014)
  • Author(s): 丸尾良浩、長崎啓祐、森麻美、松井克之、三村由卯、深見真紀、竹内義博
  • Organizer: 第117回日本小児科学会学術集会
  • Place of Presentation: 名古屋市(口演・一般)
• [Presentation] Dual oxidase 2 (DUOX2)異常症の臨床像の解明 23例の解析より (2014)
  • Author(s): 丸尾良浩、長崎啓祐、森麻美、松井克之、三村由卯、深見真紀、竹内義博
  • Organizer: 第117回日本小児科学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 小児の成長発達と内分泌 (2013)
  • Author(s): 丸尾良浩
  • Organizer: 第199回大阪小児科学会
  • Place of Presentation: 大阪市(シンポジウム)
  • Year and Date: 2013-09-29
• [Presentation] 先天性甲状腺機能低下症に対する次世代シーケンサーを用いたターゲットリシーケンス解析 (2013)
  • Author(s): 長崎啓祐、丸尾良浩、佐藤英利、小川洋平、菊池透、浅見直、深見真紀
  • Organizer: 第47回日本小児内分泌学会学術集会
  • Place of Presentation: 東京(口演・一般)
• [Presentation] AVP遺伝子に変異を認めた家族性中枢性尿崩症の2家系 (2013)
  • Author(s): 丸尾良浩、森宗孝夫、國津智彬、松井克之、森麻美、三村由卯、竹内義博
  • Organizer: 第47回日本小児内分泌学会学術集会
  • Place of Presentation: 東京(ポスター・一般)
• [Presentation] 先天性甲状腺機能低下症に対する次世代シーケンサーを用いたターゲットリシーケンス解析 (2013)
  • Author(s): 長崎啓祐、丸尾良浩、佐藤英利、小川洋平、菊池透、浅見直、深見真紀
  • Organizer: 第47回日本小児内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] AVP遺伝子に変異を認めた家族性中枢性尿崩症の２家系 (2013)
  • Author(s): 丸尾良浩、森宗孝夫、國津智彬、松井克之、森麻美、三村由卯、竹内義博
  • Organizer: 第47回日本小児内分泌学会学術集会
  • Place of Presentation: 東京
• [Presentation] Hutcinson-Gilford-Progeria Syndromeに認められた甲状腺機能低下症の検討 (2012)
  • Author(s): 丸尾良浩、川北理恵、松井克之、森麻美、森岡依子、西尾友宏、岡本暢之、宮下文、西澤嘉四郎、竹内義博
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡市(ポスター、一般)
• [Book] 大関武彦、古川漸、横田俊一郎、水口雅編、今日の小児治療指針第15版 (2012)
  • Author(s): 丸尾良浩
  • Publisher: 新生児黄疸