A comprehensive network and pathway analysis of human deafness genes.

OBJECTIVE: To perform comprehensive network and pathway analyses of the genes known to cause genetic hearing loss. STUDY DESIGN: In silico analysis of deafness genes using ingenuity pathway analysis (IPA). METHODS: Genes relevant for hearing and deafness were identified through PubMed literature searches and the Hereditary Hearing Loss Homepage. The genes were assembled into 3 groups: 63 genes that cause nonsyndromic deafness, 107 genes that cause nonsyndromic or syndromic sensorineural deafness, and 112 genes associated with otic capsule development and malformations. Each group of genes was analyzed using IPA to discover the most interconnected, that is, "nodal" molecules, within the most statistically significant networks (p < 10). RESULTS: The number of networks that met our criterion for significance was 1 for Group 1 and 2 for Groups 2 and 3. Nodal molecules of these networks were as follows: transforming growth factor beta1 (TGFB1) for Group 1, MAPK3/MAPK1 MAP kinase (ERK 1/2) and the G protein coupled receptors (GPCR) for Group 2, and TGFB1 and hepatocyte nuclear factor 4 alpha (HNF4A) for Group 3. The nodal molecules included not only those known to be associated with deafness (GPCR), or with predisposition to otosclerosis (TGFB1), but also novel genes that have not been described in the cochlea (HNF4A) and signaling kinases (ERK 1/2). CONCLUSION: A number of molecules that are likely to be key mediators of genetic hearing loss were identified through three different network and pathway analyses. The molecules included new candidate genes for deafness. Therapies targeting these molecules may be useful to treat deafness.

Complications of cochlear implantation in adults.

OBJECTIVES: We describe our experience of intraoperative and postoperative complications of cochlear implantation in an adult population. METHODS: Between April 1986 and June 2010, the senior author (A.S.) performed 449 cochlear implantations in two different institutions. Of these, 212 implantations were in adults. The operative techniques were similar in all cases. RESULTS: Complications were observed in 12 of the 212 adult cases (5.7%), of which 10 were major (4.7%) and 2 minor (1%). In 7 cases, reimplantation was necessitated by device failure (6 cases; 2.8%) or device extrusion (1 case; 0.5%). In 2 elderly patients (1%), a minor dural injury with a cerebrospinal fluid leak was controlled during the operation with temporalis fascia grafting. In 1 patient (0.5%), a subdural hematoma was observed after bipolar cauterization of a prominent diploic vein. In 2 subjects (1%), a wound infection was noted soon after implantation and was treated successfully on an outpatient basis. CONCLUSIONS: Cochlear implantation is generally a safe procedure. The most common complication was device failure. Although complications in this adult population were rather uncommon, some of them were serious, and an immediate intervention was necessary for a successful outcome.