Centronuclear myopathy in labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide

Maurer, M. et al. (2012) Centronuclear myopathy in labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide. PLoS ONE, 7(10), e46408. (doi: 10.1371/journal.pone.0046408) (PMID:23071563) (PMCID:PMC3465307)

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Abstract

Centronuclear myopathies (CNM) are inherited congenital disorders characterized by an excessive number of internalized nuclei. In humans, CNM results from ~70 mutations in three major genes from the myotubularin, dynamin and amphiphysin families. Analysis of animal models with altered expression of these genes revealed common defects in all forms of CNM, paving the way for unified pathogenic and therapeutic mechanisms. Despite these efforts, some CNM cases remain genetically unresolved. We previously identified an autosomal recessive form of CNM in French Labrador retrievers from an experimental pedigree, and showed that a loss-of-function mutation in the protein tyrosine phosphatase-like A (PTPLA) gene segregated with CNM. Around the world, client-owned Labrador retrievers with a similar clinical presentation and histopathological changes in muscle biopsies have been described. We hypothesized that these Labradors share the same PTPLA<sup>cnm</sup> mutation. Genotyping of an international panel of 7,426 Labradors led to the identification of PTPLA<sup>cnm</sup> carriers in 13 countries. Haplotype analysis demonstrated that the PTPLA<sup>cnm</sup> allele resulted from a single and recent mutational event that may have rapidly disseminated through the extensive use of popular sires. PTPLA-deficient Labradors will help define the integrated role of PTPLA in the existing CNM gene network. They will be valuable complementary large animal models to test innovative therapies in CNM.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Penderis, Professor Jacques
Authors: Maurer, M., Mary, J., Guillaud, L., Fender, M., Pelé, M., Bilzer, T., Olby, N., Penderis, J., Shelton, G.D., Panthier, J.J., Thibaud, J.-L., Barthélémy, I., Aubin-Houzelstein, G., Blot, S., Hitte, C., and Tiret, L.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Published Online:05 October 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PloS ONE 7(10):e46408
Publisher Policy:Reproduced under a Creative Commons License

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