Department of Pediatrics, Neuromuscular Division, Nationwide Children's Hospital, Columbus, Ohio, USA.
Muscle Nerve. 2010 Jul;42(1):14-21. doi: 10.1002/mus.21650.
Reports of dysferlinopathy have suggested a clinically heterogeneous group of patients. We identified specific novel molecular and phenotypic features that help distinguish dysferlinopathies from other forms of limb-girdle muscular dystrophy (LGMD). A detailed history, physical exam, and protein and mutation analysis of genomic DNA was done for all subjects. Five of 21 confirmed DYSF gene mutations were not previously reported. A distinct "bulge" of the deltoid muscle in combination with other findings was a striking feature in all patients. Six subjects had atypical calf enlargement, and 3 of these exhibited a paradoxical pattern of dysferlin expression: severely reduced by direct immunofluorescence with overexpression on Western blots. Six patients showed amyloid deposits in muscle that extended these findings to new domains of the dysferlin gene, including the C2G domain. Correlative studies showed colocalization of amyloid with deposition of dysferlin. The present data further serve to guide clinicians facing the expensive task of molecular characterization of patients with an LGMD phenotype.
肌营养不良蛋白病的报告表明，患者存在临床异质性。我们发现了一些特定的新分子和表型特征，有助于将肌营养不良蛋白病与其他类型的肢带型肌营养不良症（LGMD）区分开来。对所有受试者进行了详细的病史、体格检查以及蛋白质和基因突变的基因组 DNA 分析。21 个已确认的 DYSF 基因突变中有 5 个以前没有报道过。三角肌的明显“膨出”与其他发现相结合是所有患者的一个显著特征。6 名受试者存在非典型的小腿增大，其中 3 名表现出肌营养不良蛋白表达的矛盾模式：直接免疫荧光显示严重减少，而 Western blot 显示过度表达。6 名患者的肌肉中存在淀粉样沉积物，这些发现扩展到肌营养不良蛋白基因的新域，包括 C2G 域。相关研究显示淀粉样沉积物与肌营养不良蛋白的沉积存在共定位。目前的数据进一步有助于指导临床医生面对具有 LGMD 表型的患者进行昂贵的分子特征分析任务。
