A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation.

INTRODUCTION: Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients' manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established. METHODS: Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2. RESULTS: Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation. CONCLUSION: By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.

Wideband Tympanometry: Normative Data for Young Iranian Adults.

INTRODUCTION: The middle ear sound transmission features can impact acoustic sounds reaching the inner ear. Wideband tympanometry (WBT) or wideband acoustic immittance is an effective and desirable measurement of conductive conditions in newborns and adults and has appropriate sensitivity to distinguish different pathologies like otosclerosis from other middle ear conflicts. Recently, there has been an increased utilization of WBT, which highlights the importance of collecting population-based normative data as a necessary step in the standardization of this test, as well as for its clinical application. This study aimed to obtain normative data on WBT in the adult Iranian ethnic. METHODS: There were 101 participants (202 ears) consisting of 53 males (57.4%) and 48 females (42.6%) in the age range of 19-29 years. The Titan WBT device (Interacoustics, Assens, Denmark) was used for WBT measurements. The broadband click was utilized as the probe tone between frequencies of 250 Hz and 8,000 Hz. All the participants underwent ear, nose, and throat assessments, pure-tone audiometry, and conventional tympanometry (226 Hz). Features like equivalent ear canal volume (Veq), tympanometric peak pressure, gradient, resonance frequency (RF), energy absorbance (EA), and admittance (Ad) were tested. RESULTS: In this cross-sectional study, 202 ears were tested for WBT. EA increased by frequency enhancement; at 1 kHz and 2 kHz the EA was the most prominent; at 2,519 Hz, it started decreasing, and at 8 kHz, there was a slight increase. There was also a significant difference in the Veq and Ad between males and females. Studies have shown that the Veq may vary between male and female subjects based on body size. CONCLUSION: In this study, normative data for the WBT were obtained from young Iranian adults with normal hearing ranges and middle ear conditions. We hope that this study and the resulting norm will provide a basis for increasing the use of WBT in Iranian diagnostic and clinical practices.

Effect of transcranial direct current stimulation on short-term and long-term treatment of chronic tinnitus.

OBJECTIVE: This study was conducted to investigate the effectiveness of anodal and cathodal methods in reducing the intensity of tinnitus and to compare them with the control. METHODOLOGY: This randomized double-blind clinical trial with case and control groups was conducted in Al-Zahra Hospital in Isfahan between 2015 and 2016. In this trial, 51 patients with tinnitus, for at least one year, were selected among those outpatients visiting the throat, nose and ear clinic within this period. Inclusion criteria were patients on electrical stimulation prohibition, with Ménière's disease, otosclerosis, chronic headache, and pulsatile tinnitus. Patients were randomly divided in three equal-sized groups: anodal stimulation group, cathodal stimulation group, and control group. The subjects received 20-min current stimulation (2 mA). Five subjects were selected from those with a significant difference between the stimulated states (anodal or cathodal) and/or control. They received weekly transcranial electrical stimulation for two months, and their long-term recovery from tinnitus was investigated. Data analysis was done with SPSS20. RESULTS: Findings showed no significant between-groups difference in mean scores of tinnitus before the intervention (p = .68); whereas, this difference was significant immediately after the intervention (p = .02) and 1 h after it (p = .03). The mean score of tinnitus in the anodal stimulation group was significantly lower than the control; whereas, no significant difference was observed between the anodal and cathodal stimulation groups, and between the cathodal and control groups (p < .05). Findings also showed that the mean scores of tinnitus in two cathodal stimulation groups (p = .24) and control group (p = .62) were not significantly different at three different points of time; whereas, this score was significantly different in the anodal group at these time points (p = .01). CONCLUSION: In conclusion, anodal stimulation was more effective than the cathodal and control stimulation in reducing the intensity of tinnitus in the short term.

Comparison of Melatonin and Sertraline Therapies on Tinnitus: A Randomized Clinical Trial.

BACKGROUND: Tinnitus is the perception of noise or ringing without external acoustic stimulants which affects almost 10% of general population. Many therapies have been recommended including diet modifications, herbal remedies, and chemical drugs. Most common utilized drugs for tinnitus are melatonin and antidepressants such as sertraline which have been proven in different studies. In this study, we aimed to compare the efficacy of melatonin and sertraline in treating tinnitus for the first time. METHODS: In this clinical trial, 70 patients with tinnitus according to inclusion and exclusion criteria were included and randomly divided into two groups: melatonin group, taking melatonin 3 mg once daily and sertraline group taking sertraline 50 mg once daily, all treating for 3 months. Before and after treatments, every patient received Tinnitus Handicap Inventory (THI) questionnaire and severity of tinnitus was assessed, and data analysis was performed. RESULTS: Before treatments, the mean of THI score for melatonin and sertraline groups were 45.02 ± 17.67 and 44.85 ± 20.57, respectively. There was no significant difference between both groups THI score (P = 0.23). After 3 months, the mean of THI scores for melatonin and sertraline groups were 30.29 ± 19.62 and 36.96 ± 25.03, respectively which the mean of THI scores in two groups was decreased significantly (P < 0.01, for-both). In addition, indicated the significant decline in THI score of melatonin group who were under treatments with melatonin 3 mg once daily (P = 0.02). CONCLUSIONS: Here in this clinical trial, we demonstrated that both melatonin and sertraline are efficient in treating tinnitus, but the usage of melatonin 3 mg once daily is more effective.

Cigarette smoking effect on human cochlea responses.

BACKGROUND: Smoking is one of the most important risk factor in increasing of non-communicable disorders, especially chronic diseases such as cancer, stroke, heart and respiratory diseases. Cigarette smoking could damage the cochlea and causing hearing loss. The otoacoustic emission (OAE) is a source of information for determining cochlear responses to sound stimuli and how to change the response of the auditory system in some diseases. OAE test was sensitive to outer hair cells (OHCs) activity. MATERIALS AND METHODS: In this study, tried to evaluate a hearing threshold of the smoker group versus non-smoker ones through pure tone audiometery, transient evoked otoacoustic emission (TEOAE) and distortion product otoacoustic emission (DPOAE) tests. RESULTS: The results indicated that significant decrement of 8000 Hz threshold, reduced DPOAE/TEOAE amplitude in the smoker group than non-smoker one (P < 0.05). DPOAE amplitudes decline reflects the cochlear damage caused by smoking. CONCLUSION: OAEs test was clinically non-invasive, accurate, and objective evaluation of the performance of cochlear OHCs.