Armagan Incesulu

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

Considerable differences on the frequencies of the mitochondrial 12S rRNA A1555G and tRNASer(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.

A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy

Screening of 12 Turkish families with apparently autosomal recessive nonsyndromic sensorineural deafness without GJB2 and mtDNA m.1555A > G mutations for 11 previously mapped recessive deafness loci showed a family in which hearing loss cosegregated with the DFNB9 (OTOF) locus. Three affected children were later found to carry a novel homozygous c.3032T > C (p.Leu1011Pro) mutation in the OTOF gene. Both parents were heterozygous for the mutation. p.Leu1011Pro alters a conserved leucine residue in the C2D domain of otoferlin. Pure tone audiometry of the family showed severe to profound sensorineural hearing loss (with U‐shape audiograms) in children, and normal hearing in the parents. Otoacoustic emissions and auditory brainstem response (ABR) suggested the presence of auditory neuropathy in affected individuals.

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364–371.

Cochlear implantation in cases with incomplete partition type III (X-linked anomaly)

Incomplete partition-type III anomaly (X-linked deformity) is no common finding in a prospective candidate for cochlear implantation. In this paper, the problems about the cochlear implantation in cases with incomplete partition-type III anomaly (X-linked deformity) and profound sensorineural hearing loss is discussed. High-resolution multidedector computed tomography (MDCT) and magnetic resonance imaging were performed preoperatively in all patients. MDCT revealed that there was bulbous dilatation at the lateral ends of internal auditory canals (IAC) in all patients. There were also enlargements of labyrinthine segments of facial and superior vestibular nerve canals. Patients with the basal turns of cochlea incompletely separated from IAC were also presented. Patients with IP-type III (X-linked deformity) and profound SNHL were implanted. Standard transmastoid-facial recess approach was used and cerebrospinal gusher was encountered after the cochleostomy in all cases. Postoperative performance was very good in all patients. Two patients had complications, which are facial nerve stimulation and device failure. Both patients were reimplanted. Cochlear implantation is a good choice in the patients with IP-type III. However, this anomaly may have special potential risk than the other inner ear abnormalities. Therefore, the surgeon should be aware of them and must be ready to inform the patient and parents.

Sacculocolic reflex in patients with dementia: is it possible to use it for early diagnosis?

Alzheimer disease (AD) is a progressive, irreversible entity associated with behavioral changes, memory loss and disturbance of daily life activities. Current diagnostic tools can detect neuronal degeneration in AD only after irreversible damage that already existed. Vestibular evoked myogenic potentials (VEMP) test utilizes the sacculocolic reflex arc and has been used in neuro-otology practice for many years. In this study, we aim to determine if VEMP can be used for diagnostic purposes at the earliest stages of AD. Twenty patients with AD and ten patients with mild cognitive impairment were enrolled in this study. Control group was 30 healthy volunteers with no neurological or otological diseases. Abnormal VEMP responses were found in most of the patients at different stages of AD. VEMP test may be used for early diagnosis of AD. Also, it may provide a novel advancement in understanding of pathophysiology of this disease.

Cochlear implantation in children with inner ear malformations: report of two cases

UNLABELLED Cochlear implantation of congenitally deaf children with inner ear malformations is gaining special interest. Although the number of the reported cases is increasing, the decision for implantation needs thorough investigation. Preoperative evaluation, surgical approach and postoperative follow-up can be challenging. STUDY DESIGN A retrospective analysis of two cases with inner ear malformations. PATIENTS One patient was a 3-year-old-girl who had cochlear and cochleovestibular nerve aplasia on the left side and incomplete partition on the other side. The other patient was a 5-year-old-boy who had hypoplastic cochlea on both sides. Both of them also had vestibular anomalies. Cases were implanted by using multichannel cochlear implant. RESULTS No complications were encountered. Both patients responded to acoustic stimuli, and their speech perception skills were improved. After 10 months of cochlear implant use, their results seem encouraging. CONCLUSION Except cochlear or cochleovestibular nerve agenesis, inner ear malformations cannot be accepted as a contraindication for cochlear implantation. Although there can be difficulties during the surgery or in the postoperative period, patients with inner ear malformations can also benefit from cochlear implantation. It is essential that all possible complications and postoperative performance should be discussed with the parents.

The importance of thrombotic risk factors in the development of idiopathic sudden hearing loss

Impaired cochlear blood circulation has been suggested to cause sudden hearing loss. In this study, the role of factor V 1691 G-A (FV 1691 G-A), prothrombin 20210 G-A (PT 20210 G-A), methylene tetrahydrofolate reductase 677 C-T (MTHFR 677 C-T), factor V 4070 A-G (FV 4070 A-G), endothelial cell protein C receptor (EPCR) gene 23-bp insertion, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G mutation was assessed. Fifty-three patients with idiopathic sudden sensorineural hearing loss and 80 individuals comprising the control group were included in this study. The frequency for FV 1691 A was 6.2% in the patient group and 3.7% in the control group, PT 20210 G-A was 1.2% in the patient group and 1.9% in the control group, and FV 4070 A-G was 7.5% in the patient group and 11.3% in the control group. The frequency of MTHFR 677 C-T was significantly higher in the patient group than in the control group, with a P value of .03. PAI-1-675 4G/5G polymorphism was found to be 71.2% and 69.8%, in the control group and the patient group, respectively. The EPCR 23-bp insertion was 0% in the control group and was found in 3 patients (3.7%), which needs further study.

Investigation of the Presence of Biofilms in Chronic Suppurative Otitis Media, Nonsuppurative Otitis Media, and Chronic Otitis Media with Cholesteatoma by Scanning Electron Microscopy

Objective. Biofilms have been shown to play a major role in the pathogenesis of otolaryngologic infections. However, very limited studies have been undertaken to demonstrate the presence of biofilms in tissues from patients with chronic otitis media (COM) with or without cholesteatoma. Our objective is to study the presence of biofilms in humans with chronic suppurative and nonsuppurative otitis media and cholesteatoma. Study Design. In all, 102 tissue specimens (middle ear, mastoid tissue, and ossicle samples) were collected during surgery from 34 patients. Methods. The samples were processed for the investigation of biofilms by scanning electron microscopy (SEM). Results. Our research supports the hypothesis in which biofilms are involved in chronic suppurative otitis media, cholesteatoma, and, to a lesser degree, chronic nonsuppurative otitis media. There were higher rates in hypertrophic and granulated tissue samples than in normal mucosa. In addition, the presence of biofilms was significantly higher in the middle ear mucosa compared with the mastoid and ossicle samples. Conclusion. In the clinic, the careful use of topical or systemic antimicrobials is essential, and, during surgery, hypertrophic tissue must be carefully removed from normal tissue.

Evaluation of nasal airway alterations associated with septorhinoplasty by both objective and subjective methods

The aim of functional septorhinoplasty is to create an esthetically elegant nose and harmony in the face by preserving nasal function as well as maintaining or restoring adequate airway. Since nasal complaints are usually subjective, it may be difficult to evaluate the functions objectively. In the present study, we aimed to investigate the alterations in nasal function associated with septorhinoplasty by using both objective and subjective methods. The study population consisted of 40 patients who underwent septorhinoplasty and 40 healthy controls. Before and after the operation, visual analog scale, acoustic rhinometry, rhinomanometry, and Odiosoft-Rhino test were applied to all patients and controls. There were significant differences in all parameters both before and after the operation. While a significant difference was obtained between the patient and control groups in terms of preoperative values, no significant difference was found between postoperative values of these groups. Both objective and subjective methods are important in evaluations.

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.