Z-band alternatively spliced PDZ-motif protein (ZASP) is a sarcomeric component expressed both in cardiac and skeletal muscles. Mutations in the LDB3/ZASP gene cause cardiomyopathy and myofibrillar myopathy. We describe a c.76C>T / p.[Pro26Ser] mutation in the PDZ motif of LDB3/ZASP in two siblings exhibiting late-onset myopathy with axial, proximal and distal muscles involvement and marked variability in clinical severity in the absence of a significant family history for neuromuscular disorders. Notably, we identified involvement of the psoas muscle on MRI and muscle CT, a feature not previously documented. Proband's muscle biopsy showed an increase of ZASP expression by western blotting. Muscle fibres morphological features included peculiar sarcolemmal invaginations, pathological aggregates positive to ZASP, ubiquitin, p62 and LC3 antibodies, and the accumulation of autophagic vacuoles, suggesting that protein aggregate formation and autophagy are involved in this additional case of zaspopathy.

中文翻译：

---

Z 带选择性剪接 PDZ 基序蛋白突变家族中的蛋白质聚集体和自噬参与

Z 带交替剪接的 PDZ 基序蛋白 (ZASP) 是一种在心脏和骨骼肌中均表达的肌节成分。LDB3/ZASP 基因突变导致心肌病和肌原纤维肌病。我们描述了两个兄弟姐妹中 LDB3/ZASP 的 PDZ 基序中的 c.76C>T/p.[Pro26Ser] 突变，这些兄弟姐妹表现出迟发性肌病，伴有轴向、近端和远端肌肉受累，并且在没有显着的神经肌肉疾病家族史。值得注意的是，我们在 MRI 和肌肉 CT 上发现了腰大肌受累，这是以前没有记录的特征。先证者的肌肉活检通过蛋白质印迹显示 ZASP 表达增加。肌纤维形态特征包括特殊的肌膜内陷、ZASP阳性的病理聚集物、泛素、