Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D

James R. Mickelson; Katie M. Minor; Ling T. Guo; Steven G. Friedenberg; Jonah N. Cullen; Amanda Ciavarella; Lydia E. Hambrook; Karen M. Brenner; Sarah E. Helmond; Stanley L. Marks; G. Diane Shelton

doi:10.1186/s13395-020-00257-y

Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D

James R. Mickelson, Katie M. Minor, Ling T. Guo, Steven G. Friedenberg, Jonah N. Cullen, Amanda Ciavarella, Lydia E. Hambrook, Karen M. Brenner, Sarah E. Helmond, Stanley L. Marks, G. Diane Shelton

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8 Scopus citations

Abstract

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.

Original language	English (US)
Article number	2
Journal	Skeletal muscle
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/s13395-020-00257-y
State	Published - Dec 2021

Bibliographical note

Funding Information:
We are grateful to all owners, breeders, and clinicians who made this work possible. The authors also thank Dr. Rodger Davies, Wild Coast Veterinary Hospital, Eastern Cape, South Africa, for submitting tissue samples and clinical information.

Publisher Copyright:
© 2021, The Author(s).

Keywords

Canine
Gene mutation
Genetics
Myopathy
Sarcoglycanopathy

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title = "Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D",

abstract = "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.",

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AU - Minor, Katie M.

AU - Guo, Ling T.

AU - Friedenberg, Steven G.

AU - Cullen, Jonah N.

AU - Ciavarella, Amanda

AU - Hambrook, Lydia E.

AU - Brenner, Karen M.

AU - Helmond, Sarah E.

AU - Marks, Stanley L.

AU - Shelton, G. Diane

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PY - 2021/12

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N2 - 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.

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Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D

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