McMillan J R, Akiyama M, Rouan F, Mellerio J E, Lane E B, Leigh I M, Owaribe K, Wiche G, Fujii N, Uitto J, Eady R A J, Shimizu H
Department of Dermatology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
Muscle Nerve. 2007 Jan;35(1):24-35. doi: 10.1002/mus.20655.
Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD, MIM 226670) is caused by plectin defects. We performed mutational analysis and immunohistochemistry using EBS-MD (n = 3 cases) and control skeletal muscle to determine pathogenesis. Mutational analysis revealed a novel homozygous plectin-exon32 rod domain mutation (R2465X). All plectin/HD1-121 antibodies stained the control skeletal muscle membrane. However, plectin antibodies stained the cytoplasm of type II control muscle fibers (as confirmed by ATPase staining), whereas HD1-121 stained the cytoplasm of type I fibers. EBS-MD samples lacked membrane (n = 3) but retained cytoplasmic HD1-121 (n = 1) and plectin staining in type II fibers (n = 3). Ultrastructurally, EBS-MD demonstrated widening and vacuolization adjacent to the membrane and disorganization of Z-lines (n = 2 of 3) compared to controls (n = 5). Control muscle immunogold labeling colocalized plectin and desmin to filamentous bridges between Z-lines and the membrane that were disrupted in EBS-MD muscle. We conclude that fiber-specific plectin expression is associated with the desmin-cytoskeleton, Z-lines, and crucially myocyte membrane linkage, analogous to hemidesmosomes in skin.
伴有肌营养不良的单纯性大疱性表皮松解症（EBS-MD，MIM 226670）由网蛋白缺陷引起。我们对3例EBS-MD患者及对照骨骼肌进行了突变分析和免疫组织化学检测以确定其发病机制。突变分析发现了一种新的纯合网蛋白外显子32杆状结构域突变（R2465X）。所有网蛋白/HD1-121抗体均能标记对照骨骼肌膜。然而，网蛋白抗体标记II型对照肌纤维的细胞质（经ATP酶染色证实），而HD1-121标记I型纤维的细胞质。EBS-MD样本缺乏膜标记（n = 3），但II型纤维中保留了细胞质HD1-121标记（n = 1）和网蛋白标记（n = 3）。超微结构上，与对照（n = 5）相比，EBS-MD表现为膜附近增宽和空泡化以及Z线紊乱（3例中有2例）。对照肌肉免疫金标记显示网蛋白和结蛋白共定位于Z线与膜之间的丝状桥，而在EBS-MD肌肉中这些桥被破坏。我们得出结论，纤维特异性网蛋白表达与结蛋白细胞骨架、Z线以及至关重要的心肌细胞膜连接相关，类似于皮肤中的半桥粒。
