Desminopathies (MIM*601419) are clinically heterogeneous, manifesting with myopathy and/or cardiomyopathy and with intra-sarcoplasmic desmin-positive deposits. They have either an autosomal dominant (AD) or recessive (AR) pattern of inheritance. Desmin is a crucial intermediate filament protein regulating various cellular functions in muscle cells. Here, we report a 13-year-old girl, born of second-degree consanguineous parents, with normal developmental milestones, who presented with dilated cardiomyopathy, respiratory insufficiency and predominant distal upper limb weakness. A striking feature on muscle biopsy was the presence of a peripheral chain of nuclei in addition to myopathic features. Immunostaining showed complete lack of desmin expression, further confirmed by western blot analysis. Ultrastructurally, subsarcolemmal granular material, expanded Z-band aggregation, distortion of myofilaments, focal Z-band streaming, lobed and clustered myonuclei were observed. Next-generation sequencing revealed a novel homozygous nonsense mutation c.448C>T, p.R150X in the patient, while the parents were heterozygous carriers. Single mitochondrial DNA deletion and isolated complex IV deficiency were noted. Our findings add to the ever-expanding phenotype and molecular spectrum of desminopathies.

Desminopathies (MIM*601419) 在临床上具有异质性，表现为肌病和/或心肌病以及肌浆内结蛋白阳性沉积物。它们具有常染色体显性 (AD) 或隐性 (AR) 遗传模式。结蛋白是一种重要的中间丝蛋白，可调节肌肉细胞中的各种细胞功能。在这里，我们报告了一名 13 岁女孩，她是二级近亲父母，发育里程碑正常，表现为扩张型心肌病、呼吸功能不全和主要的上肢远端无力。肌肉活检的一个显着特征是除了肌病特征外还存在外周核链。免疫染色显示完全缺乏结蛋白表达，通过蛋白质印迹分析进一步证实。超微结构，肌膜下颗粒物质，观察到扩大的 Z 波段聚集、肌丝变形、焦点 Z 波段流、叶状和聚集的肌核。下一代测序揭示了患者中一种新的纯合无义突变 c.448C>T，p.R150X，而父母是杂合携带者。注意到单个线粒体 DNA 缺失和孤立的复合体 IV 缺陷。我们的研究结果增加了肌腱病的不断扩大的表型和分子谱。