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Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16234-9. doi: 10.1073/pnas.1209508109. Epub 2012 Sep 17.

Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers.

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  • 1Program in Genomics, Division of Genetics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

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.

PMID:
22988124
[PubMed - indexed for MEDLINE]
PMCID:
PMC3479603
Free PMC Article

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