A founder TMIE mutation is a frequent cause of hearing loss in southeastern Anatolia.

Using Affymetrix 10K arrays, we searched for regions of homozygosity in 51 Turkish families including at least three members with either congenital or prelingual autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL), and identified four families whose deafness mapped to the DFNB6 locus on 3p21 containing the TMIE gene. Mutation analysis revealed the p.R84W mutation in all four families. Screening of this mutation in 254 families with ARNSSNHL, without GJB2 mutations, revealed four additional affected families. A novel mutation was found in a non-complementary marriage between a deaf couple who were homozygous for p.R84W and p.W57X, respectively with two affected children who were compound heterozygotes. Six of the TMIE families originated from southeastern Anatolia, making p.R84W a common cause of hearing loss in that region with a relative frequency of 10.3% (95% CI is 2.5-18.1%). The overall prevalence of the p.R84W mutation in ARNSSNHL in Turkey is 2.4% (95% CI is 0.7-4.0%). Genotyping of single-nucleotide polymorphisms flanking the TMIE gene revealed a conserved haplotype, suggesting a single origin for p.R84W from a common ancestor 1250 years ago (95% CI is 650-2500 years). We conclude that p.R84W could be a common mutation in other Middle Eastern populations and should be included in mutation screening offered to individuals with ARNSSNHL.

Homozygous FGF3 mutations result in congenital deafness with inner ear agenesis, microtia, and microdontia.

Homozygous mutations in the fibroblast growth factor 3 (FGF3) gene have recently been discovered in an autosomal recessive form of syndromic deafness characterized by complete labyrinthine aplasia (Michel aplasia), microtia, and microdontia (OMIM 610706 - LAMM). In order to better characterize the phenotypic spectrum associated with FGF3 mutations, we sequenced the FGF3 gene in 10 unrelated families in which probands had congenital deafness associated with various inner ear anomalies, including Michel aplasia, with or without tooth or external ear anomalies. FGF3 sequence changes were not found in eight unrelated probands with isolated inner ear anomalies or with a cochlear malformation along with auricle and tooth anomalies. We identified two new homozygous FGF3 mutations, p.Leu6Pro (c.17T>C) and p. Ile85MetfsX15 (c.254delT), in four subjects from two unrelated families with LAMM. The p.Leu6Pro mutation occurred within the signal site of FGF3 and is predicted to impair its secretion. The c.254delT mutation results in truncation of FGF3. Both mutations completely co-segregated with the phenotype, and heterozygotes did not have any of the phenotypic findings of LAMM. Some affected children had large skin tags on the upper side of the auricles, which is a distinctive clinical component of the syndrome. Enlarged collateral emissary veins associated with stenosis of the jugular foramen were noted on computerized tomographies of most affected subjects with FGF3 mutations. However, similar venous anomalies were also detected in persons with non-syndromic Michel aplasia, suggesting that a direct causative role of impaired FGF3 signaling is unlikely.

Cochlear implantation in chronic otitis media.

Patients with chronic otitis media (COM) may have profound sensorineural hearing loss either due to the disease process or secondary to a surgical procedure. Some patients who are candidates for cochlear implantation may have COM coincidentally. The patients in this group need special attention when cochlear implantation is applied. The aim of this study is to evaluate the potential risks and complications in patients with COM. Cochlear implantation was performed in six patients with COM or an infected radical cavity and profound hearing loss. Five of them underwent a two-stage operation, and one had a single-stage operation. Cochlear implantation was performed in all patients without complications. The follow-up period was uneventful. Although such patients have some potential risks, when certain surgical rules are followed very strictly cochlear implantation can be successfully performed in patients with COM.

Frequency of mtDNA A1555G and A7445G mutations among children with prelingual deafness in Turkey.

UNLABELLED: Considerable differences on the frequencies of the mitochondrial 12S rRNA A1555G and tRNA(Ser(UCN)) A7445G mutations have been reported in different populations. Our screening of 168 patients coming from independent Turkish families with prelingual sensorineural non-syndromic deafness revealed three deaf children with A1555G (1.8%) but no examples of A7445G. One proband with the mitochondrial A1555G mutation has also evidence for right parietal infarct on a brain imaging study, for which common thrombotic mutations were found to be negative. CONCLUSION: This study shows that the mitochondrial A1555G mutation is among the significant causes of prelingual non-syndromic deafness in the Turkish population.

Moderate hearing loss and pseudodominant inheritance due to L90P/35delG mutations in the GJB2 (connexin 26) gene.

Mutations in the GJB2 (connexin 26-Cx26) gene are responsible for 20-50% of cases with prelingual non-syndromic deafness in a large part of the world including Turkey. Although most of the cases with Cx26 deafness have a recessive mode of inheritance, a small group of families demonstrated dominant or pseudodominant inheritance. In this report we present a Turkish family in which the proband had congenital profound deafness and was found to be homozygous for the 35delG mutation, whereas the father and a paternal uncle who had milder, late-onset sensorineural hearing loss had compound heterozygous 35delG and L90P mutations. This family and previous reports with the L90P mutation demonstrate that the hearing loss associated with the L90P/35delG genotype is consistently milder than that of 35delG homozygotes. GJB2 gene screening should be considered in families with seemingly dominant inheritance and late-onset moderate hearing loss.

Histologic studies of the posterior stapediovestibular joint in otosclerosis.

OBJECTIVE: To determine the prevalence of ankylosis or otosclerosis at the posterior stapediovestibular joint (SVJ) in temporal bones with otosclerosis, with special reference to stapes surgery. BACKGROUND: Long-term success of the laser stapedotomy minus prosthesis (STAMP) procedure, anterior crurotomy, and similar partial stapedectomy procedures depends on lack of ankylosis and lack of otosclerosis involving the posterior SVJ. Previous work has shown that the air-bone gap in otosclerosis correlates with narrowing and loss of the SVJ space. However, the prevalence and histologic features of otosclerotic involvement of the posterior SVJ space have not been well characterized. METHODS: Histologic assessment of serial sections through the oval window niche in 140 temporal bones with otosclerosis that had been sectioned in the axial plane (age range 20-95 years, mean 68). Bones with stapes mobilization or stapedectomy were excluded. RESULTS AND CONCLUSIONS: Two of 140 bones had otosclerosis exclusively at the posterior SVJ. Of the remaining 138 bones, all of which had otosclerosis at the anterior SVJ, 82 bones also had otosclerosis at the posterior joint. Of the 56 bones without otosclerosis of the posterior joint, there was bony ankylosis of the posterior joint in 3 bones. Thus, 53 bones (38%) had neither ankylosis nor otosclerosis involving the posterior joint, and they would be potentially suitable for a laser STAMP or a similar procedure. There was no correlation between otosclerosis at the posterior SVJ and age, sex, or duration of conductive hearing loss. Otosclerosis at the posterior joint in one ear was significantly associated with its presence at the posterior joint in the opposite ear (p = 0.01). The audiogram could not be used to reliably predict otosclerotic involvement of the posterior SVJ or the degree of footplate pathologic changes, such as ankylosis.

Correlation of acoustic threshold measures and spiral ganglion cell survival in severe to profound sensorineural hearing loss: implications for cochlear implantation.

In a temporal bone study of 26 ears from 13 patients who, in life, had severe sensorineural hearing loss, the segmental and total spiral ganglion cell (SGC) counts were correlated with hearing thresholds and with the difference between hearing thresholds in the two ears, the age at death, the duration of deafness, and the duration of hearing loss. A statistically significant correlation was found between the interaural differences in total SGC counts and the interaural difference in pure tone averages for 3, 4, and 5 frequencies. The total SGC count was higher in the ear with the better residual hearing in 11 of 12 cases. Approximately 41% of the variability in interaural difference in pure tone average was explained by the difference in SGC counts. The findings would suggest that in a given individual, selection of the ear with better residual hearing for cochlear implantation is likely to result in accessing a higher number of residual SGCs. This, in turn, may result in better speech recognition with the implant.

Revision stapedectomy: intraoperative findings, results, and review of the literature.

Seventy-four revision stapedectomies performed consecutively over 10 years (1986 to 1995) were reviewed retrospectively. The most common intraoperative findings were incus erosion, prosthesis displacement, and oval window closure. Incus erosion was more frequently associated with multiple revisions. The postoperative results were reported using the conventional method (postoperative air minus preoperative bone) as well as the guidelines recently published by the American Academy of Otolaryngology--Head and Neck Surgery (postoperative air minus postoperative bone), with success rates of postoperative air-bone gap closure to within 10 dB after revision surgery of 51.6% and 45.6%, respectively. Patients with persistent conductive hearing loss (large residual air-bone gaps) after primary stapedectomy had poorer postrevision hearing results. Sensorineural hearing loss (defined as a drop in bone pure-tone average of more than 10 dB) occurred in four cases (5.4%). The number of revision surgeries, variations in operative techniques using laser or drill, and the ossicle to which the prosthesis was attached did not statistically affect the postoperative air-bone gaps. These results were compared with previously published data.