Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D.
Canine
Gene mutation
Genetics
Myopathy
Sarcoglycanopathy
Journal
Skeletal muscle
ISSN: 2044-5040
Titre abrégé: Skelet Muscle
Pays: England
ID NLM: 101561193
Informations de publication
Date de publication:
07 01 2021
07 01 2021
Historique:
received:
22
09
2020
accepted:
14
12
2020
entrez:
7
1
2021
pubmed:
8
1
2021
medline:
18
1
2022
Statut:
epublish
Résumé
A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis. Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents. This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.
Sections du résumé
BACKGROUND
A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified.
METHODS
Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis.
RESULTS
Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents.
CONCLUSIONS
This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.
Identifiants
pubmed: 33407862
doi: 10.1186/s13395-020-00257-y
pii: 10.1186/s13395-020-00257-y
pmc: PMC7789357
doi:
Substances chimiques
Sarcoglycans
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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