Vattemi G, Neri M, Piffer S, Vicart P, Gualandi F, Marini M, Guglielmi V, Filosto M, Tonin P, Ferlini A, Tomelleri G
Department of Neurological Sciences and Vision, Section of Clinical Neurology, University of Verona, Italy.
Acta Myol. 2011 Oct;30(2):121-6.
The term myofibrillar myopathies (MFM) refers to uncommon neuromuscular disorders that pathologically are characterized by myofibrillar degeneration and ectopic expression of several proteins. MFM are partly caused by mutations in genes that encode mainly Z-disk-related proteins (desmin, alphaB-crystallin, myotilin, ZASP, filamin C and BAG3). We reviewed clinical, light and electron microscopy, immunohistochemistry, immunoblotting and genetic findings of 21 patients with MFM (15 unrelated patients and three pairs of brothers) investigated at our neuromuscular center. MFM patients begin to show symptoms at any age, from juvenile to late adult life and present a different distribution of muscle weakness. Cardiac involvement and peripheral neuropathy are common. Typical histological features include focal areas with reduction/loss of ATPase and oxidative enzyme activity, and amorphous material (eosinophilic on hematoxylin and eosin and dark blue on Engel-Gomori trichrome) in these abnormal fiber areas. Electron microscopy shows disintegration of myofibrils starting from the Z-disk and accumulation of granular and filamentous material among the myofilaments. Immunohistochemical studies demonstrate focal accumulation of desmin, alphaB-crystallin and myotilin in abnormal muscle fibers while immunoblot analysis does not highlight differences in the expression of these proteins also including ZASP protein. Therefore, unlike immunoblot, immunohistochemistry together with light and electron microscopy is a useful diagnostic tool in MFM. Finally three of our 21 patients have missense mutations in the desmin gene, two brothers carry missense mutations in the gene encoding myotilin, one has a missense mutation in alphaB-crystallin, and none harbour pathogenic variations in the genes encoding ZASP and BAG3.
肌原纤维肌病（MFM）这一术语指的是一类罕见的神经肌肉疾病，其病理特征为肌原纤维变性以及多种蛋白质的异位表达。MFM部分由主要编码与Z盘相关蛋白质（结蛋白、αB-晶状体蛋白、肌联蛋白、ZASP、细丝蛋白C和BAG3）的基因突变引起。我们回顾了在我们神经肌肉中心接受检查的21例MFM患者（15例无亲缘关系的患者和3对兄弟）的临床、光镜和电镜检查、免疫组织化学、免疫印迹及基因检测结果。MFM患者在从青少年到成年晚期的任何年龄开始出现症状，且肌无力分布各异。心脏受累和周围神经病变很常见。典型的组织学特征包括ATP酶和氧化酶活性降低/丧失的局灶性区域，以及这些异常纤维区域中的无定形物质（苏木精-伊红染色呈嗜酸性，恩格尔-戈莫里三色染色呈深蓝色）。电镜显示肌原纤维从Z盘开始解体，肌丝之间有颗粒状和丝状物质积聚。免疫组织化学研究显示结蛋白、αB-晶状体蛋白和肌联蛋白在异常肌纤维中局灶性积聚，而免疫印迹分析未突出这些蛋白质（包括ZASP蛋白）表达的差异。因此，与免疫印迹不同，免疫组织化学结合光镜和电镜检查是MFM中一种有用的诊断工具。最后，我们的21例患者中有3例在结蛋白基因中有错义突变，2对兄弟在编码肌联蛋白的基因中有错义突变，1例在αB-晶状体蛋白中有错义突变，而在编码ZASP和BAG3的基因中均未发现致病变异。
