title: Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.
abstract: Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.
authors.affiliation: Institute of Neurology, Catholic University, L.go A. Gemelli 8, 0018, Rome, Italy. m.pescatori@rm.unicatt.it
authors.forename: Mario
authors.initials: M
authors.lastname: Pescatori
authors.forename: Aldobrando
authors.initials: A
authors.lastname: Broccolini
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Adele
authors.initials: A
authors.lastname: D'amico
authors.forename: Camilla
authors.initials: C
authors.lastname: Bernardini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirabella
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Giglio
authors.forename: Anna
authors.initials: A
authors.lastname: Modoni
authors.forename: Marina
authors.initials: M
authors.lastname: Pedemonte
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tasca
authors.forename: Giuliana
authors.initials: G
authors.lastname: Galluzzi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.forename: Pietro A
authors.initials: PA
authors.lastname: Tonali
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
mesh_terms: D000367:Age Factors; D000818:Animals; D002675:Child, Preschool; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D007223:Infant; D007249:Inflammation; D051379:Mice; D009132:Muscles / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors