Gene expression analysis of human otosclerotic stapedial footplates

Abstract

Otosclerosis is a complex disease that results in a common form of conductive hearing loss due to impaired mobility of the stapes. Stapedial motion becomes compromised secondary to invasion of otosclerotic foci into the stapedio-vestibular joint. Although environmental factors and genetic causes have been implicated in this process, the pathogenesis of otosclerosis remains poorly understood. To identify molecular contributors to otosclerosis we completed a microarray study of otosclerotic stapedial footplates. Stapes footplate samples from otosclerosis and control patients were used in the analysis. One-hundred-and-ten genes were found to be differentially expressed in otosclerosis samples. Ontological analysis of differentially expressed genes in otosclerosis provides evidence for the involvement of a number of pathways in the disease process that include interleukin signaling, inflammation and signal transduction, suggesting that aberrant regulation of these pathways leads to abnormal bone remodeling. Functional analyses of genes from this study will enhance our understanding of the pathogenesis of this disease.

Mutations and altered expression ofSERPINF1in patients with familial otosclerosis

“…These were (i) a robust ‘naive pipeline’ based on retaining variants predicted to be deleterious by either PolyPhen-2 (20) or SIFT (21) and absent from dbSNP134; and (ii) a ‘candidate-gene pipeline’ where only variants in an otosclerosis candidate gene list of 494 genes were retained. The list included genes implicated in otosclerosis from association studies (22–26), gene expression studies (27), genes within linked regions of the genome (10–17,28) and genes known to be involved in other connective tissue disorders that can exhibit an otosclerosis-like hearing loss (29–33). The list also included 176 genes found to be differentially expressed in otosclerotic stapes by an RNA-seq analysis of 12 stapes (J.L.…”

Etiopathogenesis of otosclerosis

“…Although these loci have been mapped, we have little information regarding the role of these genes in disease development ( Table 2). While clinical similarities and some genetic association studies have suggested etiological relationship between otosclerosis and osteogenesis imperfecta, there is no evidence of a common genetic background in the two diseases [35,36]. Otosclerosis is rather considered as a complex bone remodeling disorder with relatively common monogenic forms [36].…”

Genetic Association and Gene Expression Profiles of TGFB1 and the Contribution of TGFB1 to Otosclerosis Susceptibility

“…Recently, microarray‐based gene expression profiling in human stapes tissue samples from OTSC cases and controls has shown the differential expression of two genes (PF4: upregulated, and IBSP: downregulated) playing roles in TGFB1 signaling . PF4 acts as an inhibitory protein that inhibits the binding of TGFB1 to type I receptors but not to type II receptors .…”