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Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Sanchez, L; Beltran, E; De Stefani, A; Guo, L T; Shea, A; Shelton, D; De Risio, L; Burmeister, L M

Authors

L Sanchez

E Beltran

A De Stefani

L T Guo

A Shea

D Shelton

L De Risio

L M Burmeister



Abstract

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog.

Citation

Sanchez, L., Beltran, E., De Stefani, A., Guo, L. T., Shea, A., Shelton, D., …Burmeister, L. M. (2018). Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs. PLoS ONE, 13(23), e0193372. https://doi.org/10.1371/journal.pone.0193372

Journal Article Type Article
Acceptance Date Feb 8, 2018
Publication Date Feb 23, 2018
Deposit Date Aug 31, 2018
Publicly Available Date Sep 4, 2018
Journal PLoS One
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 13
Issue 23
Pages e0193372
DOI https://doi.org/10.1371/journal.pone.0193372
Public URL https://rvc-repository.worktribe.com/output/1388440

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