Molecular and biochemical analysis of mutants identified in patients with RAS/MAPK syndromes.

• Project/Area Number: 21689029
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: 新堀 哲也 Tohoku University, 大学院・医学系研究科, 助教 (40436134)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000); Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2009: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 先天異常学 / ヌーナン症候群 / コステロ症候群 / CFC症候群 / RAS / MAPK症候群 / RAS/MAPK症候群 / 先天奇形症候群

Research Abstract

Mutation analysis in patients with the RAS/MAPK syndromes was performed. SHOC2 gene was analyzed in 92 patients with the RAS/MAPK syndromes. Eight patients had SHOC2_p.S2G mutation. To understand the mechanism underlying the pathogenesis of the RAS/MAPK syndromes, we performed functional analysis of RAF1 and HRAS mutants identified in the patients.

Research Products

• [Journal Article] A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. (2011)
  • Author(s): Kamada F, Aoki Y, Narisawa A, Abe Y, Komatsuzaki S, Kikuchi A, Kanno J, Niihori T, Ono M, Ishii N, Owada Y, Fujimura M, Mashimo Y, Suzuki Y, Hata A, Tsuchiya S, Tominaga T, Matsubara Y, Kure S.
  • Journal Title: J Hum Genet 56(1) Pages: 34-40
  • NAID: 10030657293
  • Peer Reviewed
• [Journal Article] A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. (2011)
  • Author(s): Kamada F, et al.
  • Journal Title: J Hum Genet. Volume: 56 Pages: 34-40
  • Peer Reviewed
• [Journal Article] A familial case of LEOPARD syndrome associated with a high-functioning autism spectrum disorder. (2010)
  • Author(s): Watanabe Y, Yano S, Niihori T, Aoki Y, Matsubara Y, Yoshino M, Matsuishi T.
  • Journal Title: Brain Dev [Epub ahead of print]
  • NAID: 10031121955
  • Peer Reviewed
• [Journal Article] Mutation analysis of the SHOC2 gene in Noonan-like syndrome and in hematologic malignancies. (2010)
  • Author(s): Komatsuzaki S, Aoki Y, Niihori T, Okamoto N, Hennekam RC, Hopman S, Ohashi H, Mizuno S, Watanabe Y, Kamasaki H, Kondo I, Moriyama N, Kurosawa K, Kawame H, Okuyama R, Imaizumi M, Rikiishi T, Tsuchiya S, Kure S, Matsubara Y.
  • Journal Title: J Hum Genet 55(12) Pages: 801-809
  • NAID: 10030737892
  • Peer Reviewed
• [Journal Article] Non-Hodgkin Lymphoma in a Patient With Cardiofaciocutaneous Syndrome. (2010)
  • Author(s): Ohtake A, Aoki Y, Saito Y, Niihori T, Shibuya A, Kure S, Matsubara Y.
  • Journal Title: J Pediatr Hematol Oncol. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders : dephosphorylation of serine 259 as the essential mechanism for mutant activation. (2010)
  • Author(s): Kobayashi T, Aoki Y, Niihori T, Cave H, Verloes A, Okamoto N, Kawame H, Fujiwara I, Takada F, Ohata T, Sakazume S, Ando T, Nakagawa N, Lapunzina P, Meneses AG, Gillessen-Kaesbach G, Wieczorek D, Kurosawa K, Mizuno S, Ohashi H, David A, Philip N, Guliyeva A, Narumi Y, Kure S, Tsuchiya S, Matsubara Y.
  • Journal Title: Hum Mutat 31(3) Pages: 284-294
  • Peer Reviewed
• [Journal Article] Non-Hodgkin Lymphoma in a Patient With Cardiofaciocutaneous Syndrome. (2010)
  • Author(s): Ohtake A, et al.
  • Journal Title: J Pediatr Hematol Oncol. Volume: (online)
  • Peer Reviewed
• [Journal Article] Mutation analysis of the SHOC2 gene in Noonan-like syndrome and inhematologic malignancies. (2010)
  • Author(s): Komatsuzaki S, et al.
  • Journal Title: J Hum Genet. Volume: 55 Pages: 801-809
  • Peer Reviewed
• [Journal Article] A familial case of LEOPARD syndrome associated with a high-functioning autism spectrum disorder. (2010)
  • Author(s): Watanabe Y, et al.
  • Journal Title: Brain Dev. Volume: (online)
  • Peer Reviewed
• [Journal Article] Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders : dephosphorylation of serine 259 as the essential mechanism for mutant activation (2010)
  • Author(s): Kobayashi T., et al.
  • Journal Title: Human Mutation 31 Pages: 284-294
  • Peer Reviewed
• [Journal Article] cardio-facio-cutaneous(CFC)症候群 (2009)
  • Author(s): 青木洋子、新堀哲也
  • Journal Title: 小児科診療 72巻増刊 Pages: 31-31
• [Journal Article] LEOPARD症候群 (2009)
  • Author(s): 青木洋子、新堀哲也
  • Journal Title: 小児科診療 72巻増刊 Pages: 60-60
• [Journal Article] Noonan症候群 (2009)
  • Author(s): 青木洋子、新堀哲也
  • Journal Title: 小児科診療 72巻増刊 Pages: 68-68
• [Presentation] Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan. (2010)
  • Author(s): Abe Y, Aoki Y, Niihori T, Ohashi H, Kurosawa K, Okamoto N, Kawame H, Mizuno S, Ogata T, Kuriyama S, Kure S, Matsubara Y.
  • Organizer: The American Society of Human Genetics 60th annual meeting.
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2010-11-05
• [Presentation] Hematologic abnormalities associated with patients with cardio-facio-cutaneous syndrome. (2010)
  • Author(s): Saito Y, Aoki Y, Niihori T, Ohtake A, Shibuya A, Sekiguchi K, Suenobu S, Izumi T, Muramatsu H, Kojima S, Kure S, Tsuchiya S, Matsubara Y.
  • Organizer: The American Society of Human Genetics 60th annual meeting.
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2010-11-05
• [Presentation] SHOC2 mutation analysis in Noonan-like syndrome and hematologic malignancies. (2010)
  • Author(s): Komatsuzaki S, Aoki Y, Niihori T, Okamoto N, Hennekam RCM, Hopman S, Ohashi H, Mizuno S, Watanabe Y, Kamasaki H, Kondo I, Moriyama N, Kurosawa K, Kawame H, Imaizumi M, Rikiishi T, Tsuchiya S, Kure S, Matsubara Y.
  • Organizer: The American Society of Human Genetics 60th annual meeting.
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2010-11-05
• [Presentation] SHOC2 mutation analysis in Noonan-like syndrome and hematologic malignancies (2010)
  • Author(s): Komatsuzaki S, et al.
  • Organizer: The American Society of Human Genetics 60^<th> annual meeting
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2010-11-05
• [Presentation] Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan (2010)
  • Author(s): Abe Y, et al.
  • Organizer: The American Society of Human Genetics 60th annual meeting
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2010-11-05
• [Presentation] Hematologic abnormalities associated with patients with cardio-facio-cutaneous syndrome (2010)
  • Author(s): Saito Y, et al.
  • Organizer: The American Society of Human Genetics 60th annual meeting
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2010-11-05
• [Presentation] Noonan症候群類縁疾患及び血液腫瘍細胞におけるSHOC2遺伝子変異解析 (2010)
  • Author(s): 小松崎匠子, ほか
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: 大宮
  • Year and Date: 2010-10-30
• [Presentation] Noonan症候群類縁疾患におけるRAF1遺伝子解析とその発症メカニズムの検討 (2010)
  • Author(s): 松原洋一、小林朋子、新堀哲也、呉繁夫、青木洋子
  • Organizer: 第17回日本遺伝子診療学会大会
  • Place of Presentation: 津
  • Year and Date: 2010-08-06
• [Presentation] CFC Syndrome with BRAF mutation at exon 15 in a patient with marked cutaneous symptoms. (2009)
  • Author(s): Nishi E. Mizuno S, Niihori T, Aoki Y, Matsubara Y.
  • Organizer: American Society of Human Genetics 59th annual meeting.
  • Place of Presentation: ワイキキ、米国
  • Year and Date: 2009-10-23
• [Presentation] CFC Syndrome with BRAF mutation at exon 15 in a patient with marked cutaneous symptoms (2009)
  • Author(s): Nishi E., et al.
  • Organizer: American Society of Human Genetics 59th annual meeting
  • Place of Presentation: ワイキキ、米国
  • Year and Date: 2009-10-23
• [Presentation] Noonan症候群類縁疾患(The RAS/MAPK syndromes)の包括的遺伝子解析 (2009)
  • Author(s): 小林朋子、青木洋子、新堀哲也、小松崎匠子、岡本伸彦、黒澤健司、川目裕、大橋博文、水野誠司、松原洋一
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] Noonan症候群類縁疾患(The RAS/MAPK syndromes)の包括的遺伝子解析 (2009)
  • Author(s): 青木洋子, ら
  • Organizer: 第16回日本遺伝子診療学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2009-08-01
• [Book] 小児の症候群 小児科診療72巻増刊 (2009)
  • Author(s): 青木洋子、新堀哲也
  • Publisher: 診断と治療社