Open AccessGlobal Gene Profiling of VCP‐associated Inclusion Body Myopathy
Author(s) -
Nalbandian Angèle,
Ghimbovschi Svetlana,
RadomAizik Shlomit,
Dec Eric,
Vesa Jouni,
Martin Barbara,
Knoblach Susan,
Smith Charles,
Hoffman Eric,
Kimonis Virginia E.
Publication year - 2012
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2012.00407.x
Subject(s) - frontotemporal dementia , myopathy , biology , bioinformatics , gene expression profiling , medicine , gene , cancer research , disease , genetics , dementia , pathology , gene expression
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. Clin Trans Sci 2012; Volume #: 1–9