Key result
Next-generation sequencing reveals a novel CASQ1 mutation in a patient with progressive upper limb weakness.
Why the study?
Only five mutations in CASQ1, a crucial sarcoplasmic reticulum calcium-binding protein in skeletal muscle, have been identified to date.
Case Report (n=1)
This first report of CASQ1-related myopathy from China identifies a novel pathogenic mutation, expanding the genetic and clinical spectrum of the disease.
Supports CASQ1 testing in atypical distal myopathies; extends the mutation spectrum but leaves open broader validation.
Calsequestrin 1 (CASQ1) is the most crucial Ca 2+ binding protein localized in the sarcoplasmic reticulum (SR) of skeletal muscle. With high capacity and low affinity for Ca 2+ , CASQ1 plays a significant role in maintaining a large amount of Ca 2+ necessary for muscle contraction. However, only five mutations in CASQ1 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 CASQ1 . 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 CASQ1 and summarized their genetic and clinical characteristics. This is the first report on CASQ1‐related myopathy from China, further expanding the mutation spectrum of CASQ1 gene and provides new insights into the function of CASQ1.
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Zhang et al. (2022) conducted a case report in CASQ1-related myopathy (n=1). Next-generation sequencing (NGS) was evaluated on Identification of CASQ1 mutation and clinical/histopathological characteristics. Next-generation sequencing revealed a novel heterozygous mutation (c.766G > A, p.Val256Met) in the CASQ1 gene in a 42-year-old Chinese female with slowly progressive upper limb weakness.
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