Pathological and molecular genetic studies on collagen VI deficient Ullrich's disease

乌尔里希病的患者有全身肌肉无力、近端关节多发性痉挛和远端关节高度伸展。最近，我们在两名Ullrich病患者的骨骼肌中发现了VI型胶原蛋白的缺失。在本研究中，我们对活检的骨骼肌进行了电子显微镜和免疫组化研究。我们发现了骨骼肌膜和毛细血管的电子显微镜异常。此外，我们还发现这些患者皮肤和培养的成纤维细胞的细胞外基质中纤维连接蛋白受体明显减少，并发现乌尔里希病患者极小的肌肉纤维显示出发育中的肌球蛋白重链和血栓调节蛋白的低表达。这些结果表明，细胞黏附异常和异常的再生或成熟过程参与了营养不良性肌肉变化的发病，至少在乌尔里希病的晚期。

Patients with Ullrich's disease have generalized muscle weakness, multiple contractures of the proximal joints and hyperextensibility of the distal joints. Recently, we found a deficiency of collagen VI protein in skeletal muscle from two patients with Ullrich's disease.In this study, we performed electron microscopic and immunohistochemical investigations on biopsied skeletal muscles. We found electron microscopic abnormalities of skeletal muscle membrane and capillaries.Furthermore we found a marked reduction of fibronectin receptors in the extracellular matrix of skin and cultured fibroblasts of these patients and found that very small muscle fibers in the patients with Ullrich's disease showed poor expression of developmental myosin heavy chain and thrombomodulin.These findings suggest that abnormality of cell adhesion and abnormal regeneration or maturation processes are involved in the pathogenesis of dystrophic muscle changes at least in the advanced stage of Ullrich's disease.