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Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report
Becker muscular dystrophy (BMD) is caused by specific mutations in the DMD gene that causes progressive muscle weakness and primarily affects skeletal and cardiac muscle. Although cardiac involvement is a significant cause of mortality in BMD, the genetic–phenotype correlation for skeletal and cardi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Singapore
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449875/ https://www.ncbi.nlm.nih.gov/pubmed/32504006 http://dx.doi.org/10.1038/s10038-020-0788-9 |
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author | Komaki, Ryouhei Hashimoto, Yasumasa Mori-Yoshimura, Madoka Oya, Yasushi Takizawa, Hotake Minami, Narihiro Nishino, Ichizo Aoki, Yoshitsugu Takahashi, Yuji |
author_facet | Komaki, Ryouhei Hashimoto, Yasumasa Mori-Yoshimura, Madoka Oya, Yasushi Takizawa, Hotake Minami, Narihiro Nishino, Ichizo Aoki, Yoshitsugu Takahashi, Yuji |
author_sort | Komaki, Ryouhei |
collection | PubMed |
description | Becker muscular dystrophy (BMD) is caused by specific mutations in the DMD gene that causes progressive muscle weakness and primarily affects skeletal and cardiac muscle. Although cardiac involvement is a significant cause of mortality in BMD, the genetic–phenotype correlation for skeletal and cardiac muscles has not been elucidated. Here, we described a 39-year-old man with BMD, who presented with subtle skeletal muscle weakness in the right leg in his 20s and underwent left ventricular restoration for severe dilated cardiomyopathy at the age of 29. He had difficulty climbing stairs after the age of 35. Neither duplication nor deletion of exons was detected by multiplex ligation-dependent probe amplification. A hemizygous c.264 + 1G>A mutation in intron 4 of the DMD was identified by next-generation sequencing. Furthermore, exon 4 skipping of the DMD was confirmed in both skeletal and cardiac muscles evaluated by reverse transcriptase PCR. Endomyocardial and skeletal muscle biopsies revealed dystrophic pathology characterized by muscle fiber atrophy and hypertrophy with a mild degree of interstitial fibrosis. Interestingly, dystrophin immunohistochemistry demonstrated patchy and faint staining of the skeletal muscle membranes but almost normal staining of the cardiac muscle membranes. Western blot analysis revealed a decreased amount of truncated dystrophin in skeletal muscle but surprisingly almost normal amount in cardiac muscle. This case indicates that BMD patients may have severe cardiac dysfunction despite preserved cardiac truncated dystrophin expression. |
format | Online Article Text |
id | pubmed-7449875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-74498752020-09-02 Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report Komaki, Ryouhei Hashimoto, Yasumasa Mori-Yoshimura, Madoka Oya, Yasushi Takizawa, Hotake Minami, Narihiro Nishino, Ichizo Aoki, Yoshitsugu Takahashi, Yuji J Hum Genet Article Becker muscular dystrophy (BMD) is caused by specific mutations in the DMD gene that causes progressive muscle weakness and primarily affects skeletal and cardiac muscle. Although cardiac involvement is a significant cause of mortality in BMD, the genetic–phenotype correlation for skeletal and cardiac muscles has not been elucidated. Here, we described a 39-year-old man with BMD, who presented with subtle skeletal muscle weakness in the right leg in his 20s and underwent left ventricular restoration for severe dilated cardiomyopathy at the age of 29. He had difficulty climbing stairs after the age of 35. Neither duplication nor deletion of exons was detected by multiplex ligation-dependent probe amplification. A hemizygous c.264 + 1G>A mutation in intron 4 of the DMD was identified by next-generation sequencing. Furthermore, exon 4 skipping of the DMD was confirmed in both skeletal and cardiac muscles evaluated by reverse transcriptase PCR. Endomyocardial and skeletal muscle biopsies revealed dystrophic pathology characterized by muscle fiber atrophy and hypertrophy with a mild degree of interstitial fibrosis. Interestingly, dystrophin immunohistochemistry demonstrated patchy and faint staining of the skeletal muscle membranes but almost normal staining of the cardiac muscle membranes. Western blot analysis revealed a decreased amount of truncated dystrophin in skeletal muscle but surprisingly almost normal amount in cardiac muscle. This case indicates that BMD patients may have severe cardiac dysfunction despite preserved cardiac truncated dystrophin expression. Springer Singapore 2020-06-05 2020 /pmc/articles/PMC7449875/ /pubmed/32504006 http://dx.doi.org/10.1038/s10038-020-0788-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Komaki, Ryouhei Hashimoto, Yasumasa Mori-Yoshimura, Madoka Oya, Yasushi Takizawa, Hotake Minami, Narihiro Nishino, Ichizo Aoki, Yoshitsugu Takahashi, Yuji Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report |
title | Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report |
title_full | Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report |
title_fullStr | Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report |
title_full_unstemmed | Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report |
title_short | Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report |
title_sort | severe cardiac involvement with preserved truncated dystrophin expression in becker muscular dystrophy by +1g>a dmd splice-site mutation: a case report |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449875/ https://www.ncbi.nlm.nih.gov/pubmed/32504006 http://dx.doi.org/10.1038/s10038-020-0788-9 |
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