Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Komaki, Ryouhei, Hashimoto, Yasumasa, Mori-Yoshimura, Madoka, Oya, Yasushi, Takizawa, Hotake, Minami, Narihiro, Nishino, Ichizo, Aoki, Yoshitsugu, Takahashi, Yuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
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
_version_ 1783574708812251136
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
work_keys_str_mv AT komakiryouhei severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT hashimotoyasumasa severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT moriyoshimuramadoka severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT oyayasushi severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT takizawahotake severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT minaminarihiro severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT nishinoichizo severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT aokiyoshitsugu severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport
AT takahashiyuji severecardiacinvolvementwithpreservedtruncateddystrophinexpressioninbeckermusculardystrophyby1gadmdsplicesitemutationacasereport