Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype.
Dog
Muscular dystrophy
Myopathy
Whole genome sequencing
Journal
Neuromuscular disorders : NMD
ISSN: 1873-2364
Titre abrégé: Neuromuscul Disord
Pays: England
ID NLM: 9111470
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
16
04
2022
revised:
30
07
2022
accepted:
05
08
2022
pubmed:
31
8
2022
medline:
2
11
2022
entrez:
30
8
2022
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 36041985
pii: S0960-8966(22)00629-0
doi: 10.1016/j.nmd.2022.08.001
pmc: PMC10040250
mid: NIHMS1883753
pii:
doi:
Substances chimiques
Dystrophin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
836-841Subventions
Organisme : NIH HHS
ID : K01 OD027058
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR064300
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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