Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
J Vet Intern Med. 2023 Nov-Dec;37(6):2504-2509. doi: 10.1111/jvim.16862. Epub 2023 Sep 14.
Two (male and female) 10-month-old American Staffordshire Terrier littermates presented for progressive weakness, joint contracture, and distal limb joint hyperlaxity beginning around 6 months of age. Neurological examination, serum creatine kinase activity, infectious disease titers, cerebrospinal fluid analysis, and electrodiagnostic testing were performed. Muscle biopsies were collected for histopathology and immunofluorescence staining for localization of dystrophy associated proteins. Whole-genome sequencing (WGS) was performed on 1 affected dog. Variants were compared to a database of 671 unaffected dogs of multiple breeds. Histopathology confirmed a dystrophic phenotype and immunofluorescence staining of muscle cryosections revealed an absence of staining for collagen-6. WGS identified a homozygous 1 bp deletion in the COL6A3 gene, unique to the first affected dog. Sanger sequencing confirmed the homozygous presence of the frameshift variant in both affected dogs. This report describes the clinical features and most likely genetic basis of an Ullrich-like recessively inherited form of congenital muscular dystrophy in American Staffordshire Terriers.
两只（公母）10 月龄的美系斯塔福梗近亲交配犬，从约 6 月龄开始出现进行性肌无力、关节挛缩和四肢远端关节过度伸展。进行了神经学检查、血清肌酸激酶活性、传染病滴度、脑脊液分析和电诊断检测。采集肌肉活检标本进行组织病理学和免疫荧光染色以定位与营养不良相关的蛋白。对 1 只患病犬进行了全基因组测序（WGS）。将变异与 671 只不同品种未受影响犬的数据库进行了比较。组织病理学证实为营养不良表型，肌肉冷冻切片的免疫荧光染色显示胶原-6 缺失。WGS 发现 COL6A3 基因中存在 1bp 的纯合缺失，该缺失仅存在于第一只受影响的犬中。Sanger 测序证实了两只受影响犬均存在纯合的移码变异。本报告描述了美系斯塔福梗中一种可能为常染色体隐性遗传的 Ullrich 样先天性肌营养不良的临床特征和最可能的遗传基础。
