Molecular diagnosis of Duchenne muscular dystrophy
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Revista Científica da Faculdade de Medicina de Campos |
Texto Completo: | https://www.fmc.br/ojs/index.php/RCFMC/article/view/130 |
Resumo: | Duchenne muscular dystrophy is the most frequent recessive X-linked genetic disease in humans, affecting 1 in 3500 born males. It is caused by mutations in the DMD gene, localized in the Xp21.2- Xp21.1 chromosomal region, which codes for dystrophin, a cytoskeleton protein found in the inner surface of muscle fibers. Pathogenic mutations are heterogeneous in nature and a considerably large number has been described. Approximately 2/3 of index cases are hereditary and the remaining 1/3 is due to de novo mutations. Direct molecular diagnosis of the etiology of the disease involves sequencing of the 79 exons for determination of mutations in affected males. This method is laborious and expensive, imiting its broad application, particularly in tracking mutation in women carriers. The identification of mutation carriers can be done indirectly by linkage analysis of microsatellites. Currently only dinucleotide microsatellites are known in 29 introns; 15o of which are used and they exhibit heterozigosity rates varying from 40 to 84% in various populations. The main drawback of genotyping dinucleotide microsatellites is the occurrence of stutter products, which differ in size by multiples of the repeat unit from the true allele. There is a need to invest in development of tetranucleotide and pentanucleotide microsatellites that result in significant reduction of stutter products and that enables accurate allele designation, diminishing the possibilities of error of diagnosis. |
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Molecular diagnosis of Duchenne muscular dystrophyDiagnóstico molecular da distrofia muscular Duchenneanálise de ligaçãodiagnóstico molecular indireto;distrofia muscular Duchennemicrossatélitesmarcadores polimórficossequenciamentoDuchenne muscular dystrophyindirect molecular diagnosis;linkage analysismicrosatellitespolymorphic markerssequencingDuchenne muscular dystrophy is the most frequent recessive X-linked genetic disease in humans, affecting 1 in 3500 born males. It is caused by mutations in the DMD gene, localized in the Xp21.2- Xp21.1 chromosomal region, which codes for dystrophin, a cytoskeleton protein found in the inner surface of muscle fibers. Pathogenic mutations are heterogeneous in nature and a considerably large number has been described. Approximately 2/3 of index cases are hereditary and the remaining 1/3 is due to de novo mutations. Direct molecular diagnosis of the etiology of the disease involves sequencing of the 79 exons for determination of mutations in affected males. This method is laborious and expensive, imiting its broad application, particularly in tracking mutation in women carriers. The identification of mutation carriers can be done indirectly by linkage analysis of microsatellites. Currently only dinucleotide microsatellites are known in 29 introns; 15o of which are used and they exhibit heterozigosity rates varying from 40 to 84% in various populations. The main drawback of genotyping dinucleotide microsatellites is the occurrence of stutter products, which differ in size by multiples of the repeat unit from the true allele. There is a need to invest in development of tetranucleotide and pentanucleotide microsatellites that result in significant reduction of stutter products and that enables accurate allele designation, diminishing the possibilities of error of diagnosis.A distrofia muscular Duchenne (DMD) é a doença genética com padrão de herança recessiva ligada ao sexo mais frequente em humanos, afetando 1 a cada 3500 meninos nascidos vivos. É causada por mutações no gene DMD, localizado na região cromossômica Xp21.2-Xp21.1, que codifica a distrofina, uma proteína do citoesqueleto encontrada na superfície interna das fibras musculares. As mutações patogênicas são de natureza heterogênea e um grande número tem sido descrito. Aproximadamente 2/3 dos casos são hereditários e 1/3 esporádicos causados por mutações de novo. O diagnóstico molecular direto da etiologia da doença envolve o sequenciamento dos 79 éxons do gene DMD para determinação de mutações em homens afetados. Este método é laborioso e dispendioso, o que limita a sua ampla aplicação, em particular no rastreio de mulheres portadoras. A identificação de portadoras pode ser feita de maneira indireta mediante análise de ligação de microssatélites pelo teste de DNA. Atualmente são conhecidos só microssatélites do tipo dinucleotídeo em 29 íntrons; 15 desses são utilizados e exibem taxas de heterozigose variando de 40 a 84% em diversas populações. O principal problema da genotipagem de microssatélites dinucleotídeos é a ocorrência de produtos stutter, que diferem em tamanho por múltiplos da unidade de repetição do alelo verdadeiro. Há necessidade de investir no desenvolvimento de microssatélites tetranucleotídeo e pentanucleotídeo que resultam em significativa redução da amplificação de produtos stutter e que possibilitam uma melhor designação alélica, diminuindo as possibilidades de erro de diagnóstico.Faculdade de Medicina de Campos (FMC)2009-06-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.fmc.br/ojs/index.php/RCFMC/article/view/13010.29184/1980-7813.rcfmc.130.vol.4.n1.2009Scientific Journal of the Medical School of Campos; Vol. 4 No. 1 (2009); 02-09Revista Científica da Faculdade de Medicina de Campos; v. 4 n. 1 (2009); 02-091980-7813reponame:Revista Científica da Faculdade de Medicina de Camposinstname:Faculdade de Medicina de Campos (FMC)instacron:FMCporhttps://www.fmc.br/ojs/index.php/RCFMC/article/view/130/101Copyright (c) 2009 Revista Científica da Faculdade de Medicina de Camposinfo:eu-repo/semantics/openAccessSarlo, Laís Gomesda Silva, Antonio Francisco AlvesMedina-Acosta, Enrique2017-08-28T22:18:58Zoai:ojs.www.fmc.br:article/130Revistahttps://www.fmc.br/ojs/index.php/RCFMC/PRIhttps://www.fmc.br/ojs/index.php/RCFMC/oai||revista@fmc.br1980-78131980-7813opendoar:2017-08-28T22:18:58Revista Científica da Faculdade de Medicina de Campos - Faculdade de Medicina de Campos (FMC)false |
dc.title.none.fl_str_mv |
Molecular diagnosis of Duchenne muscular dystrophy Diagnóstico molecular da distrofia muscular Duchenne |
title |
Molecular diagnosis of Duchenne muscular dystrophy |
spellingShingle |
Molecular diagnosis of Duchenne muscular dystrophy Sarlo, Laís Gomes análise de ligação diagnóstico molecular indireto; distrofia muscular Duchenne microssatélites marcadores polimórficos sequenciamento Duchenne muscular dystrophy indirect molecular diagnosis; linkage analysis microsatellites polymorphic markers sequencing |
title_short |
Molecular diagnosis of Duchenne muscular dystrophy |
title_full |
Molecular diagnosis of Duchenne muscular dystrophy |
title_fullStr |
Molecular diagnosis of Duchenne muscular dystrophy |
title_full_unstemmed |
Molecular diagnosis of Duchenne muscular dystrophy |
title_sort |
Molecular diagnosis of Duchenne muscular dystrophy |
author |
Sarlo, Laís Gomes |
author_facet |
Sarlo, Laís Gomes da Silva, Antonio Francisco Alves Medina-Acosta, Enrique |
author_role |
author |
author2 |
da Silva, Antonio Francisco Alves Medina-Acosta, Enrique |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Sarlo, Laís Gomes da Silva, Antonio Francisco Alves Medina-Acosta, Enrique |
dc.subject.por.fl_str_mv |
análise de ligação diagnóstico molecular indireto; distrofia muscular Duchenne microssatélites marcadores polimórficos sequenciamento Duchenne muscular dystrophy indirect molecular diagnosis; linkage analysis microsatellites polymorphic markers sequencing |
topic |
análise de ligação diagnóstico molecular indireto; distrofia muscular Duchenne microssatélites marcadores polimórficos sequenciamento Duchenne muscular dystrophy indirect molecular diagnosis; linkage analysis microsatellites polymorphic markers sequencing |
description |
Duchenne muscular dystrophy is the most frequent recessive X-linked genetic disease in humans, affecting 1 in 3500 born males. It is caused by mutations in the DMD gene, localized in the Xp21.2- Xp21.1 chromosomal region, which codes for dystrophin, a cytoskeleton protein found in the inner surface of muscle fibers. Pathogenic mutations are heterogeneous in nature and a considerably large number has been described. Approximately 2/3 of index cases are hereditary and the remaining 1/3 is due to de novo mutations. Direct molecular diagnosis of the etiology of the disease involves sequencing of the 79 exons for determination of mutations in affected males. This method is laborious and expensive, imiting its broad application, particularly in tracking mutation in women carriers. The identification of mutation carriers can be done indirectly by linkage analysis of microsatellites. Currently only dinucleotide microsatellites are known in 29 introns; 15o of which are used and they exhibit heterozigosity rates varying from 40 to 84% in various populations. The main drawback of genotyping dinucleotide microsatellites is the occurrence of stutter products, which differ in size by multiples of the repeat unit from the true allele. There is a need to invest in development of tetranucleotide and pentanucleotide microsatellites that result in significant reduction of stutter products and that enables accurate allele designation, diminishing the possibilities of error of diagnosis. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-06-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.fmc.br/ojs/index.php/RCFMC/article/view/130 10.29184/1980-7813.rcfmc.130.vol.4.n1.2009 |
url |
https://www.fmc.br/ojs/index.php/RCFMC/article/view/130 |
identifier_str_mv |
10.29184/1980-7813.rcfmc.130.vol.4.n1.2009 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://www.fmc.br/ojs/index.php/RCFMC/article/view/130/101 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2009 Revista Científica da Faculdade de Medicina de Campos info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2009 Revista Científica da Faculdade de Medicina de Campos |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Faculdade de Medicina de Campos (FMC) |
publisher.none.fl_str_mv |
Faculdade de Medicina de Campos (FMC) |
dc.source.none.fl_str_mv |
Scientific Journal of the Medical School of Campos; Vol. 4 No. 1 (2009); 02-09 Revista Científica da Faculdade de Medicina de Campos; v. 4 n. 1 (2009); 02-09 1980-7813 reponame:Revista Científica da Faculdade de Medicina de Campos instname:Faculdade de Medicina de Campos (FMC) instacron:FMC |
instname_str |
Faculdade de Medicina de Campos (FMC) |
instacron_str |
FMC |
institution |
FMC |
reponame_str |
Revista Científica da Faculdade de Medicina de Campos |
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Revista Científica da Faculdade de Medicina de Campos |
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Revista Científica da Faculdade de Medicina de Campos - Faculdade de Medicina de Campos (FMC) |
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