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

background and purposeMiyoshi 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.

methodsWe 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.

resultsA 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.

conclusionWe 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.