2007 Fiscal Year Final Research Report Summary
Molecular analysis of congenital anomaly syndromes due to mutations in signal transduction pathways
| Project/Area Number |
18390296
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
MATSUBARA Yoichi Tohoku University, Tohoku University School of Medicine, Professor (00209602)
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| Co-Investigator(Kenkyū-buntansha) |
KURE Shigeo Tohoku University School of Medicine, 大学院・医学系研究科, Associate Professor (10205221)
AOKI Yoko Tohoku University School of Medicine, 大学院・医学系研究科, Assistant Professor (80332500)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Congenital anomaly syndrome / Noonan syndrome / Costello syndrome / CFC syndrome / signal transduction / genetic mutation / oncogene |
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| Research Abstract |
We have been searching for genetic abnormalities in multiple congenital anomalies/mental retardation syndromes. Recently we identified mutations in the Ras/MAPK signaling pathways among Noonan-related syndromes, namely Costello syndrome and cardiofaciocutaenous (CFC) syndrome. The purpose of the current study is to identify novel disease-causing genes related to various signal transduction pathways, to establish genetic testing protocols, and to perform functional studies to better understand the pathogenesis of these disorders. At first, we collected DNA samples and cell cultures from patients with Noonan syndrome, Costello syndrome, CFC syndrome and patients with similar clinical pictures. We performed comprehensive mutation analysis of the previously reported disease-causing genes and reported the results in a review in Human Mutation (Published Online: May 9 2008). Candidate gene analysis revealed mutations in novel genes. Functional studies of the identified mutations were performed to characterize their effects on the signaling pathway. We also started to create transgenic mice harboring mutated HRAS gene as a disease model for Costello syndrome.
The entire study was approved by the Ethics Committee of Tohoku University School of Medicine and the genetic analysis was done according to the relevant guidelines.
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[Journal Article] Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome2007
Author(s)
Narumi Y, Aoki Y, Niihori T, Neri G, Cave H, Verloes A, Nava C, Kavamura MI, Okamoto N, Kurosawa K, Hennekam RC, Wilson LC, Gillessen-Kaesbach G, Wieczorek D, Lapunzina P, Ohashi H, Makita Y, Kondo I, Tsuchiya S, Ito E, Sameshima K, Kato K, Kure S, Matsubara Y.
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Journal Title
J Med Genet A 143
Pages: 799-807
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome2007
Author(s)
Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, Niihori T, Aoki Y, Matsubara Y, Arveiler B, Lacombe D, Pasmant E, Parfait B, Baumann C, Heron D, Sigaudy S, Toutain A, Rio M, Goldenberg A, Leheup B, Verloes A, Cave H.
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Journal Title
Am J Med Genet 44
Pages: 763-771
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Direct correlation between ischemic injury and extracellular glycine concentration in mice with genetically altered activities of the glycine cleavage multienzyme system2007
Author(s)
Oda M, Kure S, Sugawara T, Yamaguchi S, Kojima K, Shinka T, Sato K, Narisawa A, Aoki Y, Matsubara Y, Omae T, Mizoi K, Kinouchi H.
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Journal Title
Stroke 38
Pages: 2157-2164
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis2007
Author(s)
Kanno J, Kure S, Narisawa A, Kamada F, Takayanagi M, Yamamoto K, Hoshino H, Goto T, Takahashi T, Haginoya K, Tsuchiya S, Baumeister FA, Hasegawa Y, Aoki Y, Yamaguchi S, Matsubara Y.
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Journal Title
Mol Genet Metab 91
Pages: 384-389
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome2006
Author(s)
Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y.
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Journal Title
Nat Genet 38
Pages: 294-296
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension2006
Author(s)
del Toro M, Arranz JA, Macaya A, Riudor E, Raspall M, Moreno A, Vazquez E, Ortega A, Matsubara Y, Kure S, Roig M.
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Journal Title
Ann Neurol 60
Pages: 148-152
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Rapid diagnosis of glycine encephalopathy by 13C-glycine breath test2006
Author(s)
Kure S, Korman SH, Kanno J, Narisawa A, Kubota M, Takayanagi T, Takayanagi M, Saito T, Matsui A, Kamada F, Aoki Y, Ohura T, Matsubara Y.
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Journal Title
Ann Neurol 59
Pages: 862-867
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation2006
Author(s)
Kamada F, Kure S, Kudo T, Suzuki Y, Oshima T, Ichinohe A, Kojima K, Niihori T, Kanno J, Narumi Y, Narisawa A, Kato K, Aoki Y, Ikeda K, Kobayashi T, Matsubara Y.
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Journal Title
J Hum Genet 51
Pages: 455-460
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia2006
Author(s)
Kure S, Kato K, Dinopoulos A, Gail C, DeGrauw TJ, Christodoulou J, Bzduch V, Kalmanchey R, Fekete G, Trojovsky A, Plecko B, Breningstall G, Tohyama J, Aoki Y, Matsubara Y.
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Journal Title
Hum Mutat 27
Pages: 343-352
Description
「研究成果報告書概要(欧文)」より
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