CASQ1-related myopathy: The first report from China and the literature review.

Calsequestrin 1 (CASQ1) is the most crucial Ca binding protein localized in the sarcoplasmic reticulum (SR) of skeletal muscle. With high capacity and low affinity for Ca, CASQ1 plays a significant role in maintaining a large amount of Ca necessary for muscle contraction. However, only five mutations in have been identified to date. Here, we report a 42-year-old Chinese female patient who presented with a 12 years history of slowly progressive upper limb weakness, predominantly affecting distal muscles, which was uncommon comparing to other CASQ1-related patients. Next-generation sequencing (NGS) analysis revealed a novel heterozygous mutation (c.766G > A, p.Val256Met) in . Functional studies confirmed the likely pathogenicity of this variant. Muscle histopathology revealed rare optically empty vacuoles in myofibers and atypical eosinophilic granules in the cytoplasm, which has not been observed before. We also performed a literature review on all the pathogenic mutations in and summarized their genetic and clinical characteristics. This is the first report on CASQ1-related myopathy from China, further expanding the mutation spectrum of gene and provides new insights into the function of CASQ1.