title: Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a "molecular signature" in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids.
authors.affiliation: Program in Genomics, Division of Genetics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Fedik
authors.initials: F
authors.lastname: Rahimov
authors.forename: Oliver D
authors.initials: OD
authors.lastname: King
authors.forename: Doris G
authors.initials: DG
authors.lastname: Leung
authors.forename: Genila M
authors.initials: GM
authors.lastname: Bibat
authors.forename: Charles P
authors.initials: CP
authors.lastname: Emerson
authors.forename: Louis M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D016015:Logistic Models; D018482:Muscle, Skeletal / Q000378:metabolism*; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger