title: miRNA expression in control and FSHD fetal human muscle biopsies.
abstract: BACKGROUND
  Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development.
  
  
  METHODS
  Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays.
  
  
  RESULTS
  During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD.
  
  
  CONCLUSIONS
  This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France; INSERM UMRS974, Paris, France; CNRS FRE 3617, F-75013, Paris, France; Institut de Myologie, F-75013, Paris, France; Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Débora Morueco
authors.initials: DM
authors.lastname: Portilho
authors.affiliation: Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil; Laboratório de Pesquisa Clínica em DST-AIDS, Instituto de Pesquisa de Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Marcelo Ribeiro
authors.initials: MR
authors.lastname: Alves
authors.affiliation: CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
authors.forename: Gueorgui
authors.initials: G
authors.lastname: Kratassiouk
authors.affiliation: Laboratoire de Génétique Médicale et Génomique Fonctionnelle, INSERM UMRS 910, Aix Marseille Université, Faculté de Médecine de la Timone, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roche
authors.affiliation: Laboratoire de Génétique Médicale et Génomique Fonctionnelle, INSERM UMRS 910, Aix Marseille Université, Faculté de Médecine de la Timone, Marseille, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Magdinier
authors.affiliation: Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Eliane Corrêa
authors.initials: EC
authors.lastname: de Santana
authors.affiliation: CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Polesskaya
authors.affiliation: CNRS FRE 3377, Université Paris-Sud CEA Saclay, Gif-sur-Yvette, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Harel-Bellan
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France; INSERM UMRS974, Paris, France; CNRS FRE 3617, F-75013, Paris, France; Institut de Myologie, F-75013, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.affiliation: Laboratório de Pesquisas sobre o Timo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France; INSERM UMRS974, Paris, France; CNRS FRE 3617, F-75013, Paris, France; Institut de Myologie, F-75013, Paris, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Center of Research in Myology UM76, Paris, France; INSERM UMRS974, Paris, France; CNRS FRE 3617, F-75013, Paris, France; Institut de Myologie, F-75013, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dumonceaux
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D019295:Computational Biology; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000196:embryology / Q000235:genetics* / Q000473:pathology*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs