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Abstract：
OBJECTIVE: Myofibrillar myopathies (MFMs) are a group of inherited or sporadic neuromuscular disorders characterized morphologically by foci of myofibril dissolution, disintegration of the Z-disk and insoluble protein aggregates within the muscle fibres. The sequential events leading to muscle fibre damage remains largely unknown.
RESULTS: We investigated the expression and the cellular localization of RNA polymerase II (RNAPII)-associated proteins (RPAPs) in muscle biopsies from patients with genetically proven and sporadic MFMs. Our data demonstrated that RPAP2, and to a lesser extent GPN1/RPAP4, are accumulated focally in the cytoplasm of MFM muscle fibres in which they co-localize with POLR2A/RPB1, the largest subunit of RNAPII, and correspond to αB-cystallin deposits in distribution and staining intensity. No abnormal staining for RPAP2 has been observed in muscle of patients with central cores, minicores and neurogenic target fibres.
CONCLUSIONS: Together, these findings could provide new insights into the molecular pathogenesis of MFMs and suggest that RPAP2 immunostaining can be a useful diagnostic tool to depict protein aggregates in MFMs.
RESULTS: We investigated the expression and the cellular localization of RNA polymerase II (RNAPII)-associated proteins (RPAPs) in muscle biopsies from patients with genetically proven and sporadic MFMs. Our data demonstrated that RPAP2, and to a lesser extent GPN1/RPAP4, are accumulated focally in the cytoplasm of MFM muscle fibres in which they co-localize with POLR2A/RPB1, the largest subunit of RNAPII, and correspond to αB-cystallin deposits in distribution and staining intensity. No abnormal staining for RPAP2 has been observed in muscle of patients with central cores, minicores and neurogenic target fibres.
CONCLUSIONS: Together, these findings could provide new insights into the molecular pathogenesis of MFMs and suggest that RPAP2 immunostaining can be a useful diagnostic tool to depict protein aggregates in MFMs.
摘要：
目的：肌原纤维性肌病（MFM）是一组遗传性或偶发性神经肌肉疾病，其形态学特征为肌原纤维溶解灶，Z盘的崩解和肌纤维内的不溶性蛋白质聚集体。导致肌纤维损伤的顺序事件在很大程度上仍然未知。
结果：我们研究了RNA聚合酶II（RNAPII）相关蛋白（RPAP）在患有遗传证明和散发性MFM的患者的肌肉活检中的表达和细胞定位。我们的数据表明，RPAP2，以及在较小程度上GPN1/RPAP4，在MFM肌纤维的细胞中聚集，它们与最大的RNRAP2A/PB1共同定位在分布和染色强度上对应于αB-cystallin沉积物。在有中央核心的患者的肌肉中未观察到RPAP2的异常染色，微小核和神经源性靶纤维。
结论：一起，这些发现可以为了解MFM的分子发病机制提供新的见解，并表明RPAP2免疫染色可以成为描述MFM中蛋白质聚集体的有用诊断工具。
结果：我们研究了RNA聚合酶II（RNAPII）相关蛋白（RPAP）在患有遗传证明和散发性MFM的患者的肌肉活检中的表达和细胞定位。我们的数据表明，RPAP2，以及在较小程度上GPN1/RPAP4，在MFM肌纤维的细胞中聚集，它们与最大的RNRAP2A/PB1共同定位在分布和染色强度上对应于αB-cystallin沉积物。在有中央核心的患者的肌肉中未观察到RPAP2的异常染色，微小核和神经源性靶纤维。
结论：一起，这些发现可以为了解MFM的分子发病机制提供新的见解，并表明RPAP2免疫染色可以成为描述MFM中蛋白质聚集体的有用诊断工具。
