Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A

• DOI: 10.1371/journal.pone.0003750
• Publication Date: 2008-11-17T23:55:07Z
• Authors: Amets Sáenz; Margarita Azpitarte; Rubén Armañanzas; France Leturcq; Ainhoa Alzualde; Iñaki Inza; Federico García-B...; Gaspar De la Herran; Julián Corcuera; Ana Cabello; Carmen Navarro; Carolina De la Torre; Eduard Gallardo; Isabel Illa; Adolfo López de M...
• Keywords: Limb-girdle muscular dystrophy; Dysferlin

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain plays different roles cells, but little known about its functions or vivo substrates. The aim of this study was to identify the genes showing an altered expression LGMD2A patients and possible pathways they are implicated in. Ten muscle samples from with which molecular diagnosis ascertained were investigated using array technology analyze gene profiling as compared ten normal samples. Upregulated mostly those related extracellular matrix (different collagens), cell adhesion (fibronectin), development (myosins melusin) signal transduction. It therefore suggested that proteins located participating costameric region processes regulated during skeletal development. Genes ubiquitin proteasome degradation pathway found be deregulated patients, suggesting regulation may under control activity. As frizzled-related protein (FRZB) upregulated samples, it could hypothesized β-catenin also at Wnt signaling pathway, leading incorrect myogenesis. Conversely, most transcription factor downregulated (MYC, FOS EGR1). Finally, upregulation IL-32 immunoglobulin induce eosinophil chemoattraction explaining inflammatory findings observed presymptomatic stages. obtained results try shed some light on identification novel therapeutic targets for limb-girdle dystrophies.