Mátyás
Fakultäten » Medizinische Fakultät » Medizinische Molekulargenetik, Institut für » PD Dr. Gabor Matyas » Mátyás
Completed research project
| Title / Titel | Molecular basis of Marfan syndrome: In silico, in vitro, and candidate gene analyses | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | Classical Marfan syndrome (MFS, MIM 154700) is an autosomal dominant connective tissue disorder, which displays variable manifestations in the cardiovascular, ocular, and skeletal systems. Aortic aneurysms and dissections are the life-threatening events, which can be prevented by timely cardiovascular surgery. Many of the features of MFS show overlap with signs of related disorders, such as MFS type 2 (MFS2 MIM 154705), Loeys-Dietz aortic aneurysm syndrome (LDS, MIM 609192), familial thoracic aortic aneurysms and dissections (TAAD, MIM 132900), and the rare arterial tortuosity syndrome (ATS, MIM 208050). MFS is usually caused by mutations in the fibrillin-1 (FBN1) gene. Recently, heterozygous mutations in the TGFBR1 and TGFBR2 genes have been reported in MFS2, LDS, and TAAD as well as homozygous SLC2A10 mutations in ATS. The genetic diagnosis by mutation screening of the respective genes is an important prerequisite for early diagnosis, patient management, and counseling of the families. We have established a diagnostic protocol in order to detect disease-causing mutations in the respective genes in an efficient manner. By using MLPA (multiplex ligation-dependent probe amplification) and SNP array CGH (comparative genomic hybridization), we detected large genomic deletions encompassing the FBN1 locus. These findings provide evidence for true haploinsufficiency in MFS. For characterization of novel disease-associated mutations in the known genes, we use different bioinformatic tools as well as experimental systems. In addition, we examine candidate genes in order to identify the disease-causing mutation in patients who were negative upon mutation screening in the genes mentioned above. Weitere Informationen |
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| Publications / Publikationen | Magyar I, Colman D, Arnold E, Baumgartner D, Bottani A, Fokstuen S, Addor M-C, Berger W, Carrel T, Steinmann B, Mátyás G* (2009) Quantitative sequence analysis of FBN1 premature termination codons provides evidence for incomplete NMD in leukocytes. Hum Mutat 30:1355–1364Pilop C, Aregger F, Gorman RC, Brunisholz R, Gerrits B, Schaffner T, Gorman JH, Mátyás G, Carrel T, Frey BM (2009) Proteomic analysis in aortic media of patients with Marfan syndrome reveals increased activity of calpain 2 in aortic aneurysms. Circulation 120:983-991Matyas G, Alonso S, Patrignani A, Marti M, Arnold E, Magyar I, Henggeler C, Carrel T, Steinmann B, Berger W (2007) Large genomic fibrillin-1 (FBN1) gene deletions provide evidence for true haploinsufficiency in Marfan syndrome. Hum Genet 122:23-32Matyas G, Arnold E, Carrel T, Baumgartner D, Boileau C, Berger W, Steinmann B (2006) Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. Hum Mutat 27:760-769Baumgartner C, Matyas G, Steinmann B, Baumgartner D (2005) Marfan syndrome: A diagnostic challenge caused by phenotypic and genetic heterogeneity. Methods Inf Med 44:487-497Baumgartner D, Baumgartner C, Matyas G, Steinmann B, Loffler-Ragg J, Schermer E, Schweigmann U, Baldissera I, Frischhut B, Hess J, Hammerer I (2005) Diagnostic power of aortic elastic properties in young patients with Marfan syndrome. J Thorac Cardiovasc Surg 129:730-739Weitere Informationen | ||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Forschungskredit der Universität Zürich, Nachwuchsförderungskredit der Universität Zürich, SNF (Personen- und Projektförderung), Foundation |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Nov 2004 to Apr 2011 |