Beckers Evy, Cornelis Ine, Bhatti Sofie F M, Smets Pascale, Shelton G Diane, Guo Ling T, Peelman Luc, Broeckx Bart J G
Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
Small Animal Department, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
Animals (Basel). 2022 Oct 25;12(21):2928. doi: 10.3390/ani12212928.
(1) Feline dystrophin-deficient muscular dystrophy (ddMD) is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles and is caused by variants in the DMD gene. To date, only two feline causal variants have been identified. This study reports two cases of male Maine coon siblings that presented with muscular hypertrophy, growth retardation, weight loss, and vomiting. (2) Both cats were clinically examined and histopathology and immunofluorescent staining of the affected muscle was performed. DMD mRNA was sequenced to identify putative causal variants. (3) 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. mRNA sequencing revealed a nonsense variant in exon 11 of the feline DMD gene, NC_058386.1 (XM_045050794.1): c.1180C > T (p.(Arg394*)), which results in the loss of the majority of the dystrophin protein. Perfect X-linked segregation of the variant was established in the pedigree. (4) ddMD was described for the first time in the Maine coon and the c.1180C>T variant was confirmed as the causal variant.
(1) 猫科动物肌营养不良蛋白缺乏性肌营养不良（ddMD）是一种致命疾病，其特征为骨骼肌进行性无力和退化，由DMD基因变异引起。迄今为止，仅鉴定出两个猫科动物致病变异。本研究报告了两例雄性缅因库恩猫兄弟，它们出现肌肉肥大、生长发育迟缓、体重减轻和呕吐症状。(2) 对两只猫均进行了临床检查，并对受影响的肌肉进行了组织病理学和免疫荧光染色。对DMD mRNA进行测序以鉴定可能的致病变异。(3) 两只猫的血清肌酸激酶活性均显著升高。肌肉样本的肌电图和组织病理学检查显示出与营养不良表型一致的异常。免疫组织化学检测显示肌营养不良蛋白缺失，证实了肌营养不良蛋白缺乏性肌营养不良的诊断。mRNA测序揭示了猫科动物DMD基因NC_058386.1（XM_045050794.1）第11外显子中的一个无义变异：c.1180C>T（p.(Arg394*)），这导致了大部分肌营养不良蛋白的缺失。在系谱中确定了该变异的完美X连锁分离。(4) 在缅因库恩猫中首次描述了ddMD，并且c.1180C>T变异被确认为致病变异。
