title: Differential DNA methylation of the D4Z4 repeat in patients with FSHD and asymptomatic carriers.
abstract: OBJECTIVE
  We investigated the link between DNA hypomethylation and clinical penetrance in facioscapulohumeral dystrophy (FSHD) because hypomethylation is moderate and heterogeneous in patients and could not thus far be correlated with disease presence or severity.
  
  
  METHODS
  To investigate the link between clinical signs of FSHD and DNA methylation, we explored 95 cases (37 FSHD1, 29 asymptomatic individuals carrying a shortened D4Z4 array, 9 patients with FSHD2, and 20 controls) by implementing 2 approaches: methylated DNA immunoprecipitation and sodium bisulfite sequencing.
  
  
  RESULTS
  Both methods revealed statistically significant differences between asymptomatic carriers or controls and individuals with clinical FSHD, especially in the proximal region of the repeat. Absence of clinical expression in asymptomatic carriers is associated with a level of methylation similar to controls.
  
  
  CONCLUSIONS
  We provide a proof of concept that the targeted approaches that we describe could be applied systematically to patient samples in routine diagnosis and suggest that local hypomethylation within D4Z4 might serve as a modifier for clinical expression of FSHD phenotype.
  
  
  METHODS
  This study provides Class III evidence that assays for hypomethylation within the D4Z4 region accurately distinguish patients with FSHD from individuals with D4Z4 contraction without FSHD.
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Gaillard
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roche
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Dion
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Tasmadjian
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Bouget
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Salort-Campana
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vovan
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Charlene
authors.initials: C
authors.lastname: Chaix
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Broucqsault
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Morere
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Puppo
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bartoli
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levy
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Rafaëlle
authors.initials: R
authors.lastname: Bernard
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Shahram
authors.initials: S
authors.lastname: Attarian
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: From Aix Marseille Universite (M.-C.G., S.R., C.D., A.T., G.B., E.S.-C., N.B., J.M., F.P., M.B., N.L., R.B., S.A., K.N., F.M.), INSERM GMGF UMR S_910, Marseille; and APHM, Centre de Référence des Maladies Neuromusculaires et de la SLA (E.S.-C., S.A.), and APHM, Laboratoire de Génétique Médicale (C.V., C.C., N.L., R.B., K.N.), Hôpital de la Timone, Marseille, France. frederique.magdinier@univ-amu.fr.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Magdinier
mesh_terms: D000328:Adult; D002894:Chromosomes, Human, Pair 4; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D055815:Young Adult