Desmin‐related myopathy with mallory body–like inclusions is caused by mutations of the selenoprotein N gene

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Abstract
Desmin‐related myopathies (DRMs) are a heterogeneous group of muscle disorders, morphologically defined by intrasarcoplasmic aggregates of desmin. Mutations in the desmin and the α‐B crystallin genes account for approximately one third of the DRM cases. The genetic basis of the other forms remain unknown, including the early‐onset, recessive form with Mallory body–like inclusions (MB‐DRMs), first described in five related German patients. Recently, we identified the selenoprotein N gene (SEPN1) as responsible for SEPN‐related myopathy (SEPN‐RM), a unique early‐onset myopathy formerly divided in two different nosological categories: rigid spine muscular dystrophy and the severe form of classical multiminicore disease. The finding of Mallory body–like inclusions in two cases of genetically documented SEPN‐RM led us to suspect a relationship between MB‐DRM and SEPN1. In the original MB‐DRM German family, we demonstrated a linkage of the disease to the SEPN1 locus (1p36), and subsequently a homozygous SEPN1 deletion (del 92 nucleotide −19/+73) in the affected patients. A comparative reevaluation showed that MB‐DRM and SEPN‐RM share identical clinical features. Therefore, we propose that MB‐DRM should be categorized as SEPN‐RM. These findings substantiate the molecular heterogeneity of DRM, expand the morphological spectrum of SEPN‐RM, and implicate a necessary reassessment of the nosological boundaries in early‐onset myopathies. Ann Neurol 2004
Funding Information
  • Institut National de la Santé et de la Recherche Médicale (National Institut of Health and Medical Research, ISERM)
  • Association Française contre les Myopathies (French Association against Myopathies, AFM)
  • Florence R.C. Murray Fellowship Program at The Children's Hospital of Philadelphia

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