Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome
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Publication Date: | 2011 |
Other Authors: | , , |
Format: | Article |
Language: | eng |
Source: | Repositório Institucional da UNIFESP |
Download full: | http://repositorio.unifesp.br/handle/11600/6574 http://dx.doi.org/10.1590/S0100-879X2011007500095 |
Summary: | Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported. |
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Teixeira, L.v.s.Mandelbaum, Karina LezirovitzPereira, L.v.Ana Beatriz Alvarez [UNIFESP]Universidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)2015-06-14T13:43:13Z2015-06-14T13:43:13Z2011-08-01Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 44, n. 8, p. 793-800, 2011.0100-879Xhttp://repositorio.unifesp.br/handle/11600/6574http://dx.doi.org/10.1590/S0100-879X2011007500095S0100-879X2011000800009.pdfS0100-879X201100080000910.1590/S0100-879X2011007500095WOS:000294122500009WOS:000295721600014Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.Universidade de São Paulo Hospital das Clínicas, Faculdade de Medicina Instituto de BiociênciaUniversidade de São Paulo Hospital das Clínicas, Faculdade de Medicina Laboratório de Otorrinolaringologia/LIM32Universidade Federal de São Paulo (UNIFESP) Departamento de Morfologia e Genética Centro de Genética MédicaUNIFESP, Depto. de Morfologia e Genética Centro de Genética MédicaSciELO793-800engAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological ResearchMarfan syndromeFibrillin-1; TGF-βGenetic heterogeneityCandidate gene linkage analysis indicates genetic heterogeneity in Marfan syndromeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALS0100-879X2011000800009.pdfapplication/pdf491442${dspace.ui.url}/bitstream/11600/6574/1/S0100-879X2011000800009.pdf32a22485785573a640b0899076e87f31MD51open accessTEXTS0100-879X2011000800009.pdf.txtS0100-879X2011000800009.pdf.txtExtracted texttext/plain26290${dspace.ui.url}/bitstream/11600/6574/2/S0100-879X2011000800009.pdf.txta3d427d9e77aa2fb8f53612fd4740356MD52open access11600/65742022-02-08 17:45:32.098open accessoai:repositorio.unifesp.br:11600/6574Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:07:33.794783Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
title |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
spellingShingle |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome Teixeira, L.v.s. Marfan syndrome Fibrillin-1; TGF-β Genetic heterogeneity |
title_short |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
title_full |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
title_fullStr |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
title_full_unstemmed |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
title_sort |
Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome |
author |
Teixeira, L.v.s. |
author_facet |
Teixeira, L.v.s. Mandelbaum, Karina Lezirovitz Pereira, L.v. Ana Beatriz Alvarez [UNIFESP] |
author_role |
author |
author2 |
Mandelbaum, Karina Lezirovitz Pereira, L.v. Ana Beatriz Alvarez [UNIFESP] |
author2_role |
author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Teixeira, L.v.s. Mandelbaum, Karina Lezirovitz Pereira, L.v. Ana Beatriz Alvarez [UNIFESP] |
dc.subject.eng.fl_str_mv |
Marfan syndrome Fibrillin-1; TGF-β Genetic heterogeneity |
topic |
Marfan syndrome Fibrillin-1; TGF-β Genetic heterogeneity |
description |
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-08-01 |
dc.date.accessioned.fl_str_mv |
2015-06-14T13:43:13Z |
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2015-06-14T13:43:13Z |
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Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 44, n. 8, p. 793-800, 2011. |
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http://repositorio.unifesp.br/handle/11600/6574 http://dx.doi.org/10.1590/S0100-879X2011007500095 |
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0100-879X |
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S0100-879X2011000800009.pdf |
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10.1590/S0100-879X2011007500095 |
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WOS:000294122500009 WOS:000295721600014 |
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Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 44, n. 8, p. 793-800, 2011. 0100-879X S0100-879X2011000800009.pdf S0100-879X2011000800009 10.1590/S0100-879X2011007500095 WOS:000294122500009 WOS:000295721600014 |
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