ICCFGG 2022
#4 A nonsense variant in the DMD gene causes X-linked muscular dystrophy in the Maine Coon cat Bart J.G. Broeckx1* , Evy Beckers1, Ine Cornelis2, Sofie F.M. Bhatti2, Pascale Smets2, G. Diane Shelton3, Ling T. Guo3, Luc Peelman1* These authors contributed equally to this work. Bart.Broeckx@UGent.be 1Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Belgium, 2Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Belgium, 3Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California, USA Duchenne muscular dystrophy (DMD) is one of the most common inherited neuromuscular diseases in humans and is characterized by progressive weakness and degeneration of skeletal muscles. This X-linked recessive disease is caused by variants in the DMD gene, most of which are deletions resulting in frameshifts that render dystrophin non- or dysfunctional. Muscular dystrophies with a similar phenotype as DMD have been described in cats, but contrary to the large number of variants known to cause DMD, only two feline causal variants have been iden- tified to date. This study reports two cases of male Maine coon siblings that were presented with muscular hypertrophy, growth retardation, weight loss, and vomiting. Both cats showed a significant increase in serum creatine kinase activity. Electromyography and histopathological examination of the muscle samples revealed abnormalities consistent with a dystrophic phenotype. Immunohistochemical testing revealed the absence of dystrophin, confirming the diagnosis of dystrophin-deficient muscular dystrophy. The causal variant was identified as NC_058386.1 (XM_045050794.1): c.1180C>T (p.(Arg394*)), a nonsense variant in exon 11 of the feline DMD gene, which results in the loss of the majority of the dystrophin protein. Perfect X-linked segregation of the variant was established in the pedigree. The phenotypic similarities between the Maine coon siblings described in this study and DMD-affected humans support a natural animal model for human DMD.
56
Made with FlippingBook - Online magazine maker