Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy
Paula Triana-Fonseca,1 Juan Fernando Parada-Márquez,1 Claudia T Silva-Aldana,2 Daniela Zambrano-Arenas,1 Laura Lucia Arias-Gomez,2 Natalia Morales-Fonseca,3 Esteban Medina-Méndez,2 Carlos M Restrepo,4 Daniel Felipe Silgado-Guzmán,2 Dora Janeth Fonseca-Mendoza4 1Facultad de Medicina, Universidad del...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-10-01
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| Series: | The Application of Clinical Genetics |
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| Online Access: | https://www.dovepress.com/genetic-profile-of-the-dystrophin-gene-reveals-new-mutations-in-colomb-peer-reviewed-fulltext-article-TACG |
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| author | Triana-Fonseca P Parada-Márquez JF Silva-Aldana CT Zambrano-Arenas D Arias-Gomez LL Morales-Fonseca N Medina-Méndez E Restrepo CM Silgado-Guzmán DF Fonseca-Mendoza DJ |
| author_facet | Triana-Fonseca P Parada-Márquez JF Silva-Aldana CT Zambrano-Arenas D Arias-Gomez LL Morales-Fonseca N Medina-Méndez E Restrepo CM Silgado-Guzmán DF Fonseca-Mendoza DJ |
| author_sort | Triana-Fonseca P |
| collection | DOAJ |
| description | Paula Triana-Fonseca,1 Juan Fernando Parada-Márquez,1 Claudia T Silva-Aldana,2 Daniela Zambrano-Arenas,1 Laura Lucia Arias-Gomez,2 Natalia Morales-Fonseca,3 Esteban Medina-Méndez,2 Carlos M Restrepo,4 Daniel Felipe Silgado-Guzmán,2 Dora Janeth Fonseca-Mendoza4 1Facultad de Medicina, Universidad del Bosque, Bogotá, DC, Colombia; 2Department of Molecular Diagnosis, Genética Molecular de Colombia SAS, Bogotá, DC, Colombia; 3Department of Medicine, Instituto Colombiano de Neurociencias, Bogotá, DC, Colombia; 4Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, DC, ColombiaCorrespondence: Dora Janeth Fonseca-Mendoza; Daniel Felipe Silgado Guzmán Email dora.fonseca@urosario.edu.co; dansilgado@hotmail.comBackground: Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common human dystrophinopathies with recessive X-linked inheritance. Dystrophin gene deletions and duplications are the most common mutations, followed by point mutations. The aim of this study is to characterize the mutational profile of the dystrophin gene in Colombian patients with DMD/BMD.Material and Methods: Mutational profiling was determined in 69 affected patients using Sanger sequencing, next-generation sequencing (NGS) and/or multiplex ligation dependent-probes amplification (MLPA). Genetic variants were classified according to molecular consequence and new variants were determined through database and literature analysis.Results: Mutational profile in affected patients revealed that large deletions/duplications analyzed by MLPA accounted for 72.5% of all genetic variations. By using Sanger sequencing or NGS, we identified point mutations in 15.9% and small deletions in 11.6% of the patients. New mutations were found, most of them were point mutations or small deletions (10.1%).Conclusion: Our results described the genetic profile of the dystrophin gene in Colombian patients with DMD and contribute to efforts to identify molecular variants in Latin American populations. For our population, 18.8% of cases could be treated with FDA or MDA approved molecular therapies based on specific mutations. These data contribute to the establishment of appropriate genetic counseling and potential treatment.Keywords: Duchenne–Becker muscular dystrophy, DMD, MLPA, next-generation sequencing, target molecular therapy, exon skipping, mutation |
| first_indexed | 2024-12-20T00:47:06Z |
| format | Article |
| id | doaj.art-4b938f09672441be890801d51e15d04e |
| institution | Directory Open Access Journal |
| issn | 1178-704X |
| language | English |
| last_indexed | 2024-12-20T00:47:06Z |
| publishDate | 2021-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | The Application of Clinical Genetics |
| spelling | doaj.art-4b938f09672441be890801d51e15d04e2022-12-21T19:59:22ZengDove Medical PressThe Application of Clinical Genetics1178-704X2021-10-01Volume 1439940869334Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular DystrophinopathyTriana-Fonseca PParada-Márquez JFSilva-Aldana CTZambrano-Arenas DArias-Gomez LLMorales-Fonseca NMedina-Méndez ERestrepo CMSilgado-Guzmán DFFonseca-Mendoza DJPaula Triana-Fonseca,1 Juan Fernando Parada-Márquez,1 Claudia T Silva-Aldana,2 Daniela Zambrano-Arenas,1 Laura Lucia Arias-Gomez,2 Natalia Morales-Fonseca,3 Esteban Medina-Méndez,2 Carlos M Restrepo,4 Daniel Felipe Silgado-Guzmán,2 Dora Janeth Fonseca-Mendoza4 1Facultad de Medicina, Universidad del Bosque, Bogotá, DC, Colombia; 2Department of Molecular Diagnosis, Genética Molecular de Colombia SAS, Bogotá, DC, Colombia; 3Department of Medicine, Instituto Colombiano de Neurociencias, Bogotá, DC, Colombia; 4Center for Research in Genetics and Genomics – CIGGUR, GENIUROS Research Group, School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá, DC, ColombiaCorrespondence: Dora Janeth Fonseca-Mendoza; Daniel Felipe Silgado Guzmán Email dora.fonseca@urosario.edu.co; dansilgado@hotmail.comBackground: Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common human dystrophinopathies with recessive X-linked inheritance. Dystrophin gene deletions and duplications are the most common mutations, followed by point mutations. The aim of this study is to characterize the mutational profile of the dystrophin gene in Colombian patients with DMD/BMD.Material and Methods: Mutational profiling was determined in 69 affected patients using Sanger sequencing, next-generation sequencing (NGS) and/or multiplex ligation dependent-probes amplification (MLPA). Genetic variants were classified according to molecular consequence and new variants were determined through database and literature analysis.Results: Mutational profile in affected patients revealed that large deletions/duplications analyzed by MLPA accounted for 72.5% of all genetic variations. By using Sanger sequencing or NGS, we identified point mutations in 15.9% and small deletions in 11.6% of the patients. New mutations were found, most of them were point mutations or small deletions (10.1%).Conclusion: Our results described the genetic profile of the dystrophin gene in Colombian patients with DMD and contribute to efforts to identify molecular variants in Latin American populations. For our population, 18.8% of cases could be treated with FDA or MDA approved molecular therapies based on specific mutations. These data contribute to the establishment of appropriate genetic counseling and potential treatment.Keywords: Duchenne–Becker muscular dystrophy, DMD, MLPA, next-generation sequencing, target molecular therapy, exon skipping, mutationhttps://www.dovepress.com/genetic-profile-of-the-dystrophin-gene-reveals-new-mutations-in-colomb-peer-reviewed-fulltext-article-TACGduchenne-becker muscular dystrophydmdmlpanext-generation sequencingtarget molecular therapyexon skippingmutation |
| spellingShingle | Triana-Fonseca P Parada-Márquez JF Silva-Aldana CT Zambrano-Arenas D Arias-Gomez LL Morales-Fonseca N Medina-Méndez E Restrepo CM Silgado-Guzmán DF Fonseca-Mendoza DJ Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy The Application of Clinical Genetics duchenne-becker muscular dystrophy dmd mlpa next-generation sequencing target molecular therapy exon skipping mutation |
| title | Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy |
| title_full | Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy |
| title_fullStr | Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy |
| title_full_unstemmed | Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy |
| title_short | Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy |
| title_sort | genetic profile of the dystrophin gene reveals new mutations in colombian patients affected with muscular dystrophinopathy |
| topic | duchenne-becker muscular dystrophy dmd mlpa next-generation sequencing target molecular therapy exon skipping mutation |
| url | https://www.dovepress.com/genetic-profile-of-the-dystrophin-gene-reveals-new-mutations-in-colomb-peer-reviewed-fulltext-article-TACG |
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