Ferreiro, AnaAnaFerreiroGroote, CCDCCDGrooteMarks, J. J.J. J.MarksGoemans, N.N.GoemansSchreiber, GudrunGudrunSchreiberHanefeld, FolkerFolkerHanefeldFardeau, M.M.FardeauMartin, J. J.J. J.MartinGoebel, Hans H.Hans H.GoebelRichard, P.P.RichardGuicheney, P.P.GuicheneyBönnemann, Carsten G.Carsten G.Bönnemann2018-11-072018-11-072004https://resolver.sub.uni-goettingen.de/purl?gro-2/48346Desmin-related myopathies (DRMs) are a heterogeneous group of muscle disorders, morphologically defined by intrasar-coplasmic aggregates of desmin. Mutations in the desmin and the alpha-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 SEPNI locus (lp36), and subsequently a homozygous SEPNI 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.journal_article10.1002/ana.2007715122708000221115800011