A novel homozygous variant in DYSF gene is associated with Autosomal Recessive Limb Girdle Muscular Dystrophy R2/2B

Mutations in the DYSF gene, encoding dysferlin, are responsible for Limb Girdle MuscularDystrophy type R2/2B (LGMDR2/2B), Miyoshi myopathy (MM), and Distal Myopathy with AnteriorTibialis onset (MDAT). The size of the gene and the reported inter and intra familial phenotypic variability make early diagnosis difficult. Genetic analysis was conducted using Next Gene Sequencing(NGS), with a panel of 40 Muscular Dystrophies associated genes we designed. In the present study,we report a new missense variant c.5033G>A, p.Cys1678Tyr (NM_003494) in the exon 45 of DYSFgene related to Limb Girdle Muscular Dystrophy type R2/2B in a 57-year-old patient affected withLGMD from a consanguineous family of south Italy. Both healthy parents carried this variant inheterozygosity. Genetic analysis extended to two moderately affected sisters of the proband, showedthe presence of the variant c.5033G>A in both in homozygosity. These data indicate a probablepathological role of the variant c.5033G>A never reported before in the onset of LGMDR2/2B, pointing at the NGS as powerful tool for identifying LGMD subtypes. Moreover, the collection and thenetworking of genetic data will increase power of genetic-molecular investigation, the managementof at-risk individuals, the development of new therapeutic targets and a personalized medicine.