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Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype

A form of dystrophinopathy with mild or subclinical neuromuscular signs has been previously reported in a family of Labrador retrievers. Markedly and persistently elevated creatine kinase activity was first noted at 6 months of age. Skeletal muscle biopsies revealed a dystrophic phenotype, with dyst...

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Autores principales: Shelton, G. Diane, Minor, Katie M., Vieira, Natassia M., Kunkel, Louis M., Friedenberg, Steven G., Cullen, Jonah N., Guo, Ling T., Zatz, Mayana, Mickelson, James R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040250/
https://www.ncbi.nlm.nih.gov/pubmed/36041985
http://dx.doi.org/10.1016/j.nmd.2022.08.001
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author Shelton, G. Diane
Minor, Katie M.
Vieira, Natassia M.
Kunkel, Louis M.
Friedenberg, Steven G.
Cullen, Jonah N.
Guo, Ling T.
Zatz, Mayana
Mickelson, James R.
author_facet Shelton, G. Diane
Minor, Katie M.
Vieira, Natassia M.
Kunkel, Louis M.
Friedenberg, Steven G.
Cullen, Jonah N.
Guo, Ling T.
Zatz, Mayana
Mickelson, James R.
author_sort Shelton, G. Diane
collection PubMed
description A form of dystrophinopathy with mild or subclinical neuromuscular signs has been previously reported in a family of Labrador retrievers. Markedly and persistently elevated creatine kinase activity was first noted at 6 months of age. Skeletal muscle biopsies revealed a dystrophic phenotype, with dystrophin non-detectable on western blotting and immunohistochemical staining, and with increased utrophin expression. In this report we demonstrate with western blotting that α-dystroglycan is present at essentially normal levels. Whole genome sequencing has also now revealed an approximately 400kb tandem genomic DNA duplication including exons 2-7 of the DMD gene that was inserted into intron 7 of the wild type gene. Skeletal muscle cDNA from 2 cases contained DMD transcripts as expected from an in-frame properly-spliced exon 2-7 tandem insertion. A similar 5’ duplication involving DMD exons 2-7 has been reported in a human family with dilated cardiomyopathy but without skeletal myopathy. This is the 3(rd) confirmed mutation in the DMD gene in Labrador retrievers.
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spelling pubmed-100402502023-03-26 Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype Shelton, G. Diane Minor, Katie M. Vieira, Natassia M. Kunkel, Louis M. Friedenberg, Steven G. Cullen, Jonah N. Guo, Ling T. Zatz, Mayana Mickelson, James R. Neuromuscul Disord Article A form of dystrophinopathy with mild or subclinical neuromuscular signs has been previously reported in a family of Labrador retrievers. Markedly and persistently elevated creatine kinase activity was first noted at 6 months of age. Skeletal muscle biopsies revealed a dystrophic phenotype, with dystrophin non-detectable on western blotting and immunohistochemical staining, and with increased utrophin expression. In this report we demonstrate with western blotting that α-dystroglycan is present at essentially normal levels. Whole genome sequencing has also now revealed an approximately 400kb tandem genomic DNA duplication including exons 2-7 of the DMD gene that was inserted into intron 7 of the wild type gene. Skeletal muscle cDNA from 2 cases contained DMD transcripts as expected from an in-frame properly-spliced exon 2-7 tandem insertion. A similar 5’ duplication involving DMD exons 2-7 has been reported in a human family with dilated cardiomyopathy but without skeletal myopathy. This is the 3(rd) confirmed mutation in the DMD gene in Labrador retrievers. 2022-10 2022-08-06 /pmc/articles/PMC10040250/ /pubmed/36041985 http://dx.doi.org/10.1016/j.nmd.2022.08.001 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) )
spellingShingle Article
Shelton, G. Diane
Minor, Katie M.
Vieira, Natassia M.
Kunkel, Louis M.
Friedenberg, Steven G.
Cullen, Jonah N.
Guo, Ling T.
Zatz, Mayana
Mickelson, James R.
Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
title Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
title_full Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
title_fullStr Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
title_full_unstemmed Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
title_short Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
title_sort tandem duplication within the dmd gene in labrador retrievers with a mild clinical phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040250/
https://www.ncbi.nlm.nih.gov/pubmed/36041985
http://dx.doi.org/10.1016/j.nmd.2022.08.001
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