Colocalization of ribonuclear inclusions with muscle blind like-proteins in a family with myotonic dystrophy type 2 associated with a short CCTG expansion

Abstract

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystemic disorder caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. We present a three first-degree relative Italian family (proband, his mother and his sister) with a mild DM2 phenotype associated with a short (CCTG)100 expansion as far as regards the proband and his mother, while his sister shows larger expansion correlated to a more severe phenotype. FISH analysis with (CAGG)5 probe demonstrated that nuclear foci of mutant RNA were present in the proband muscle and co-localized with muscleblind-like proteins, determining their sequestration in the nucleus. This is one of the smallest expansion reported and the shortest with the evidence of nuclear foci. These data contribute to the clinical and molecular correlation of ZNF9 gene short expansion