Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype
| Autor: | G. Diane Shelton, Katie M. Minor, Natassia M. Vieira, Louis M. Kunkel, Steven G. Friedenberg, Jonah N. Cullen, Ling T. Guo, Mayana Zatz, James R. Mickelson |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Duchenne/ Becker Muscular Dystrophy
Myopathy Intellectual and Developmental Disabilities (IDD) Clinical Sciences Medical Physiology CÃO GOLDEN RETRIEVER Dystrophin Rare Diseases Dogs Dog Genetics 2.1 Biological and endogenous factors Animals Humans Muscular Dystrophy Aetiology Muscle Skeletal Genetics (clinical) Pediatric Neurology & Neurosurgery Neurosciences Skeletal Exons Duchenne Introns Brain Disorders Muscular Dystrophy Duchenne Phenotype Neurology Whole genome sequencing Musculoskeletal Pediatrics Perinatology and Child Health Muscle Neurology (clinical) |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Neuromuscular disorders : NMD, vol 32, iss 10 |
| ISSN: | 0960-8966 |
| DOI: | 10.1016/j.nmd.2022.08.001 |
| Popis: | 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 3rd confirmed mutation in the DMD gene in Labrador retrievers. |
| Databáze: | OpenAIRE |
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