Global Gene Profiling of VCP‐associated Inclusion Body Myopathy
Year: 2012
Type: article
Study design: Observational Study
Abstract: Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder caused by mutations in the Valosin-containing protein (VCP) gene on chromosome 9p12-13. Patients demonstrate limb girdle muscle weakness, which eventually progresses to involve respiratory muscles, and death from respiratory and cardiac failure. This is the first investigation to analyze key molecular mediators and signaling cascades in skeletal muscle causing myopathy by global gene microarray in hopes of understanding the dysregulated genes and molecular mechanisms underlying IBMPFD and the hope of finding novel therapeutic targets. We determined expression profiles using Human Genome Array microarray technology in Vastus lateralis muscles from patients and their first-degree relatives. We analyzed gene annotations by Database for Annotation, Visualization and Integration Discovery and identified differentially dysregulated genes with roles in several novel biological pathways, including regulation of actin cytoskeleton, ErbB signaling, cancer, in addition to regulation of autophagy, and lysosomal signaling, known disrupted pathways in VCP disease. In this report, we present data from the first global microarray analyzing IBMPFD patient muscles and elucidating dysregulated pathways to further understand the pathogenesis of the disease and discover potential therapeutics.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Deutsches Krebsforschungszentrum, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, University of California, Irvine, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research
Awards: G2483903516, Imaging Brain Function/Structure in Presymptomatic FTD, Institute for Clinical and Translational Science, Translational Studies in VCP Inclusion Body Myopathy with Paget Disease of Bone, Genetic basis of myopathy with Paget disease of bone, IDDRC at Children's Research Institute, NCMRR-DC Core Molecular & Functional Outcome Measures in Rehabilitation Medicine
OpenAlex ID: W2166162205