Detección de mutaciones causantes de distrofia muscular de Duchenne/Becker: reacción en cadena de la polimerasa multiplex vs. amplificación múltiple dependiente de ligación por sondas

Huaman-Dianderas, Francia; Guevara‐Fujita, Maria Luisa; Málaga, Diana Rojas; Estrada-Cuzcano, Alejandro; Fujita, Ricardo

doi:10.17843/rpmesp.2019.363.4085

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…De los 40 pacientes con diagnostico presuntivo de DMD/DMB, se encontró que el 45% presento alguna deleción del gen DMD de la distrofina. Un estudio realizado en el 2019 en 40 pacientes con diagnostico presuntivo de DMD/DMB encontró que el 37.5% presentaron una o más deleciones de exones del gen DMD (12). Otro estudio en el 2021 realizado en 152 pacientes con sospecha de distrofia muscular encontraron que 125 tuvieron alguna mutación del gen DMD, de los cuales 41.6% presentaron deleciones, 16% duplicaciones y el 42,4% mutaciones puntuales (13).…”

Section: Discussionunclassified

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Características clínicas y moleculares de pacientes con distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen, Perú, 1997-2007

Barriga¹

2022

rpe

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Introducción: Las distrofias musculares de Duchenne (DMD) y Becker (DMB) son enfermedades de herencia recesiva ligada al cromosoma X, por variantes en el gen de la distrofina. En Perú, existen estudios en población pediátrica sobre DMD/DMB. Objetivo: Describir las características clínicas y moleculares de pacientes con distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen, 1997-2007. Metodología: Estudio observacional, descriptivo y transversal. Se revisaron historias clínicas de pacientes admitidos en el servicio de Citogenética y Citopatología. Se diseño una ficha de recolección para recoger información de datos sociodemográficos edad y sexo, y la segunda sección de datos clínicos y moleculares. Para los análisis estadísticos se usó el paquete SPSS v.13. Resultados: De las 93 historias clínicas de pacientes con sospecha diagnóstica de distrofias musculares. Se encontró que 40 pacientes (43%) tenían diagnóstico clínico de DMD. De los cuales, 18 pacientes tenían un estudio molecular de mPCR positivo de deleción en uno o más exones del gen de la distrofina. En los pacientes con deleción de distrofina, casi todos fueron del sexo masculino y la edad promedio de diagnóstico fue de 6,5 ± 1,63 años. Conclusion: Se encontro que aproximadamente cuatro de cada diez de los pacientes con distrofias tuvieron diagnostico clinico de DMD. En el estudio molecular por mPC , casi la mitad tuvieron resultado positivo de deleción de uno o más exones del gen DMD.

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Section: Discussionunclassified

“…Por otro lado, la Sociedad Peruana de Neurología público en el 2022 la guía de práctica clínica para el diagnóstico y tratamiento de la DMD. Algunos estudios realizados en pacientes con DMD han reportado entre el 37,5% y 57,6% presentaron deleciones de uno o más exones del gen DMD (12,13).…”

Section: Introductionunclassified

Características clínicas y moleculares de pacientes con distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen, Perú, 1997-2007

Barriga¹

2022

rpe

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Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy

Triana-Fonseca¹,

Parada-Márquez²,

Silva-Aldana³

et al. 2021

TACG

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Background 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.

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Theragnosis for Duchenne Muscular Dystrophy

et al. 2021

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Dystrophinopathies cover a spectrum of rare progressive X-linked muscle diseases, arising from DMD mutations. They are among the most common pediatric muscular dystrophies, being Duchenne muscular dystrophy (DMD) the most severe form. Despite the fact that there is still no cure for these serious diseases, unprecedented advances are being made for the development of therapies for DMD. Some of which are already conditionally approved: exon skipping and premature stop codon read-through. The present work aimed to characterize the mutational spectrum of DMD in an Argentinian cohort, to identify candidates for available pharmacogenetic treatments and finally, to conduct a comparative analysis of the Latin American (LA) frequencies of mutations amenable for available DMD therapies. We studied 400 patients with clinical diagnosis of dystrophinopathy, implementing a diagnostic molecular algorithm including: MLPA/PCR/Sanger/Exome and bioinformatics. We also performed a meta-analysis of LA’s metrics for DMD available therapies. The employed algorithm resulted effective for the achievement of differential diagnosis, reaching a detection rate of 97%. Because of this, corticosteroid treatment was correctly indicated and validated in 371 patients with genetic confirmation of dystrophinopathy. Also, 20 were eligible for exon skipping of exon 51, 21 for exon 53, 12 for exon 45 and another 70 for premature stop codon read-through therapy. We determined that 87.5% of DMD patients will restore the reading frame with the skipping of only one exon. Regarding nonsense variants, UGA turned out to be the most frequent premature stop codon observed (47%). According to the meta-analysis, only four LA countries (Argentina, Brazil, Colombia and Mexico) provide the complete molecular algorithm for dystrophinopathies. We observed different relations among the available targets for exon skipping in the analyzed populations, but a more even proportion of nonsense variants (∼40%). In conclusion, this manuscript describes the theragnosis carried out in Argentinian dystrophinopathy patients. The implemented molecular algorithm proved to be efficient for the achievement of differential diagnosis, which plays a crucial role in patient management, determination of the standard of care and genetic counseling. Finally, this work contributes with the international efforts to characterize the frequencies and variants in LA, pillars of drug development and theragnosis.

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Detección de mutaciones causantes de distrofia muscular de Duchenne/Becker: reacción en cadena de la polimerasa multiplex vs. amplificación múltiple dependiente de ligación por sondas

Cited by 3 publications

References 15 publications

Características clínicas y moleculares de pacientes con distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen, Perú, 1997-2007

Características clínicas y moleculares de pacientes con distrofia muscular de Duchenne y de Becker en el Hospital Nacional Guillermo Almenara Irigoyen, Perú, 1997-2007

Genetic Profile of the Dystrophin Gene Reveals New Mutations in Colombian Patients Affected with Muscular Dystrophinopathy

Theragnosis for Duchenne Muscular Dystrophy

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