Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.
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.
Pescatori
Mario
M
Institute of Neurology, Catholic University, L.go A. Gemelli 8, 0018, Rome, Italy. m.pescatori@rm.unicatt.it
Broccolini
Aldobrando
A
Minetti
Carlo
C
Bertini
Enrico
E
Bruno
Claudio
C
D'amico
Adele
A
Bernardini
Camilla
C
Mirabella
Massimiliano
M
Silvestri
Gabriella
G
Giglio
Vincenzo
V
Modoni
Anna
A
Pedemonte
Marina
M
Tasca
Giorgio
G
Galluzzi
Giuliana
G
Mercuri
Eugenio
E
Tonali
Pietro A
PA
Ricci
Enzo
E
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