A novel biallelic mutation in the DYSF gene as a cause of Miyoshi myopathy.

BACKGROUND AND PURPOSE: Miyoshi myopathy is an autosomal recessive distal myopathy resulting from pathogenic variants in the DYSF gene encoding dysferlin. This study aimed to characterize a novel biallelic DYSF gene mutation as a cause of Miyoshi myopathy through comprehensive clinical, genetic and pathological analysis. METHODS: We evaluated serum muscle enzymes and electromyography for myopathic features and performed muscle magnetic resonance imaging to characterize the pattern of involvement. We then conducted whole-exome sequencing with Sanger validation to identify potential causative variants and obtained a muscle biopsy for pathological confirmation. RESULTS: A 19-year-old male presented with progressive bilateral lower limb weakness and symmetric posterior calf muscles atrophy. Markedly elevated creatine kinase (18053 U/L) and myopathic electromyography supported a diagnosis of distal myopathy. Muscle imaging demonstrated severe gastrocnemius atrophy without inflammation. Whole-exome sequencing identified a novel homozygous nonsense variant in exon 20 of the DYSF gene (c.1851 C > G, p.Tyr617Ter), producing a premature stop codon. Muscle biopsy confirmed absent sarcolemmal dysferlin expression, supporting a loss-of-function mechanism. CONCLUSION: We reported a novel pathogenic variant in the DYSF gene, expanding the mutational spectrum of Miyoshi myopathy and reinforcing the role of biallelic DYSF mutations in disease inheritance.