PDF(Pubmed)
Abstract：
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.
摘要：
两名（男性和女性）10个月大的美国斯塔福德郡小猎犬因逐渐虚弱而出现，关节挛缩,远端肢体关节过度松弛始于6个月大。神经系统检查,血清肌酸激酶活性，传染病滴度，脑脊液分析,并进行电诊断测试。收集肌肉活检用于组织病理学和免疫荧光染色以定位营养不良相关蛋白。对1只受影响的狗进行全基因组测序(WGS)。将变体与多个品种的671只未受影响的狗的数据库进行比较。组织病理学证实了营养不良表型，肌肉冷冻切片的免疫荧光染色显示没有胶原蛋白6染色。WGS在COL6A3基因中发现了一个纯合的1bp缺失，唯一的第一个受影响的狗。Sanger测序证实了在两个受影响的狗中存在移码变体的纯合。本报告描述了美国斯塔福德郡猎犬的Ullrich样隐性遗传性先天性肌营养不良的临床特征和最可能的遗传基础。
