Oct 2, 2012 - to 49% and 64%, respectively, in some populations (2). Although possible ..... locus harboring the IDI2 gene and its homolog IDI1 is associated with amyotrophic ... cysteine peptidase), BAK1 (BCL2-antagonist/killer 1), TRP53.
Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers Fedik Rahimova,b,1, Oliver D. Kingb,c,1, Doris G. Leungd,e, Genila M. Bibatd, Charles P. Emerson, Jr.b,c, Louis M. Kunkela,b,f,2, and Kathryn R. Wagnerd,e,g,2 a Program in Genomics, Division of Genetics, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115; bThe Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center and cBoston Biomedical Research Institute, Watertown, MA 02472; dHugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MD 21205; Departments of eNeurology and gNeuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21205; and fThe Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA 02115
Contributed by Louis M. Kunkel, June 4, 2012 (sent for review May 24, 2012)
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
