Genetic landscape of hearing loss in prelingual deaf patients of eastern Iran: Insights from exome sequencing analysis.

Hearing loss is one of the most prevalent genetic disorders in humans. Locus and allelic heterogeneity cause fundamental challenges in hearing loss genetic diagnosis and management of patients and their families. This study examined the genetic profile of patients with prelingual hearing loss who were referred to the Genetic Foundation of Khorasan Razavi spanning over a decade. Deleterious variants in GJB2 were evaluated through Sanger sequencing among 745 non-syndromic hearing loss patients. Furthermore, exome sequencing was applied in 250 patients with negative GJB2 sequencing results and 30 patients with syndromic hearing loss. The findings revealed a relatively low frequency of GJB2 variants among the studied patients. Exome sequencing successfully identified the genetic causes of hearing loss in 70% of the patients. Moreover, variants in 10 genes, namely SLC26A4, MYO15A, TMPRSS3, TMC1, OTOF, CDH23, PJVK, MYO7A, TECTA, and PCDH15, accounted for 66% of the positive exome sequencing findings in this study. At least three prevalent founder alleles in the hearing-impaired population of eastern Iran were identified. This study emphasizes the efficiency of exome sequencing as a powerful tool for determining the etiology of prelingual hearing loss in the eastern Iranian population.

Intratympanic Steroid for the Management of Sudden Hearing Loss: Introduction of a Tapering Method.

INTRODUCTION: Sudden sensorineural hearing loss (SSNHL) is a therapeutic challenge. There are several controversies regarding the management protocol of SSNHL. This study aimed to present the results of a novel treatment algorithm, which is a combination of systemic steroids and a tapering intratympanic (IT) dexamethasone regimen. MATERIALS AND METHODS: The past 10 years' medical records of idiopathic SSNHL cases in Ghaem and Emamreza hospital, Mashhad University of Medical Sciences were evaluated. Patients were assessed using standardized methods for pure-tone threshold audiometry. The management method of SSNHL treatment included oral steroids combined with IT administration of dexamethasone once a day for 7 days and continuing it on an alternate day and then weekly basis. Patients' recovery was assessed using Siegel's criteria. RESULTS: This study included a total of 248 cases of idiopathic sudden hearing loss, with a mean age of 40.63±16.19 years. In total, 105 (42.3%) and 143 (57.7%) patients were female and male, respectively. The most common associated symptoms included tinnitus (86.9%, n=205) followed by vertigo (52.1%, n=122). The final hearing outcome of patients showed that 39 (15.7%), 38(15.3%), 86 (34.7%), and 85 (34.3%) patients underwent a complete recovery, partial recovery, slight recovery, and no recovery, based on Siegel's criteria. CONCLUSIONS: The dose, interval, and duration of IT steroid treatment were not universally approved. The treatment method designed based on a tapering of IT steroid injection in combination with already known systemic administration of steroids can be a treatment option in SSNHL patients.

Investigation of MYO15A and MYO7A Mutations in Iranian Patients with Nonsyndromic Hearing Loss.

BACKGROUND: Hearing loss (HL) is the most common sensory disorder in humans, which affects individuals in both inherited and acquired forms. MYO15A and MYO7A gene mutations have a significant role in the development of deafness. In this study, we assessed the prevalence of MYO15A and MYO7A mutations in one hundred non-relative deaf Iranians. Materials and methods: The existence of MYO15A and MYO7A mutations were assessed using the tetra-primer ARMS-PCR method, High Resolution Melting (HRM) and sequencing method. Results: A heterozygote missense mutation, p.V2135L (c.6403G > T) in the MYO15A gene, was found in a patient using the sequencing method. Conclusion: These results explain the negligible prevalence of selected mutations among Iranian patients. Identifying common mutations in patients of an ethnic group can reduce the financial costs and time needed for identifying the causes of deafness.

Mutation Screening of KCNQ1 and KCNE1 Genes in Iranian Patients With Jervell and Lange-Nielsen Syndrome.

Background: Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive genetic disease with deafness and QT prolongation. Mutations in KCNQ1 and KCNE1 genes are a cause of JLNS. Our objective was to perform mutational analysis of the KCNQ1 and KCNE1 genes to determine the frequency of mutations in the Iranian population. Material and methods: Fourteen patients and their families were investigated. Mutational screening of the KCNQ1 and KCNE1 genes was performed by a polymerase chain reaction (PCR) followed by direct Sanger sequencing. Results: We identified two frameshift mutations in the KCNQ1 gene, including a novel mutation, c.1356 1356delG, and a known mutation, c.1534_1534delG. A common single nucleotide polymorphism (SNP), c.112G > A, was also found in KCNE1 in seven probands. Conclusion: A novel mutation in the KCNQ1 gene is described. There may be less frequency of mutations in the KCNQ1 and of KCNE1 genes in Iranian JLNS patients compared with other populations.

A National Iranian Cochlear Implant Registry (ICIR): cochlear implanted recipient observational study.

BACKGROUND AND OBJECTIVE: Patients who receive cochlear implants (CIs) constitutes a significant population in Iran. This population needs regular monitor on long-term outcomes, educational placement and quality of life. Currently, there is no national or regional registry on the long term outcomes of CI users in Iran. The present study aims to introduce the design and implementation of a national patient-outcomes registry on CI recipients for Iran. This Iranian CI registry (ICIR) provides an integrated framework for data collection and sharing, scientific communication and collaboration inCI research. METHODS: The national ICIR is a prospective patient-outcomes registry for patients who are implanted in one of Iranian centers. The registry is based on an integrated database that utilizes a secure web-based platform to collect response data from clinicians and patient's proxy via electronic case report forms (e-CRFs) at predefined intervals. The CI candidates are evaluated with a set of standardized and non-standardized questionnaires prior to initial device activation(as baseline variables) and at three-monthly interval follow-up intervals up to 24 months and annually thereafter. RESULTS: The software application of the ICIR registry is designed in a user-friendly graphical interface with different entry fields. The collected data are categorized into four subsets including personal information, clinical data, surgery data and commission results. The main parameters include audiometric performance of patient, device use, patient comorbidities, device use, quality of life and health-related utilities, across different types of CI devices from different manufacturers. CONCLUSION: The ICIR database could be used by the increasingly growing network of CI centers in Iran. Clinicians, academic and industrial researchers as well as healthcare policy makers could use this database to develop more effective CI devices and better management of the recipients as well as to develop national guidelines.

Comparative Study of Hearing Impairment among Healthy and Intensive Care unit Neonates in Mashhad, North East Iran.

INTRODUCTION: According to World Health Organization (WHO) 2001 statistics, hearing disorders are the most common congenital disease, and the incidence rate among high-risk newborns is as much as ten times as high as that in healthy neonates. However, 78% of screening test failures are well-baby nursery babies. The Joint Committee on Infants' Hearing (JCIH) has emphasized the importance of early diagnosis and treatment in neonates with hearing impairments in order to preserve their maximum linguistic skills. The aim of our study was to compare the prevalence of hearing loss among babies in the neonatal intensive care unit (NICU) and the rooming-in unit (RIU). MATERIALS AND METHODS: Neonates born in three hospitals in Mashhad between 2008 to 2010 were studied prospectively and screened for auditory disorders using the oto acoustic emission (OAE) test at the time of discharge and 3 weeks later. To confirm hearing loss, the auditory steady state response (ASSR) test was used among those participants who failed both OAE tests. RESULTS: Two-thousand and sixty-three neonates from the NICU were screened and compared with a control group consisting of 8,724 neonates from the RIU or the well-baby nursery. At the end of the study, hearing impairment as confirmed by failure in the ASSR test was diagnosed in 31 neonates (26 in the control group [0.30%] and five in the NICU group [1.94%]). CONCLUSION: In our study, the prevalence of hearing disorders among NICU neonates was 6.5-times greater than that among babies from the RIU or well-baby unit. This observation demonstrates the importance of universal screening programs particularly for high-risk population neonates.

Ophthalmic disturbances in children with sensorineural hearing loss.

Co-incidence of sensorineural hearing loss and ophthalmic abnormalities has a tremendous influence on development of children. This study was done to determine the nature and prevalence of ophthalmic disturbances in children with congenital sensorineural hearing loss. In a descriptive cross-sectional study, complete ophthalmologic examinations such as assessment of visual acuity, cycloplegic refraction, ocular motility examination, slit lamp examination and indirect funduscopy on 50 children with sensorineural hearing loss (determined by ABR), were performed. Thirty-two percent of cases had at least one kind of ophthalmic disturbances. Refractive errors were the most common abnormalities (28%), including astigmatism (12%), myopia and astigmatism (8%), and hyperopia (8%). Three (6%) cases had ocular motility disturbance including one case of esotropia, one case of exophoria and one case of exotropia. Twenty-four percent of cases had retinal abnormalities, including suspected Rubella retinopathy (6%), pigmentary changes suspect to retinitis pigmentosa (4%), optic nerve hypoplasia (4%), and finally poor fovea reflex (10%).

Hearing loss in Behçet syndrome.

OBJECTIVE: To determine the prevalence and characteristics of hearing loss in Behçet syndrome. STUDY DESIGN AND SETTING: This study included 27 patients with Behçet syndrome and 35 sex-and age-matched controls. A complete audiological evaluation was performed. RESULTS: The average pure-tone audiograms from both groups showed a statistically significant hearing loss in the Behçet group. Sixteen patients (59.26%) showed some degrees of sensorineural hearing loss (SNHL), with the high-frequency type (4, 8, 10, and 12 kHz) being the most common pattern (93.75%). Hearing loss was the fourth most common manifestation. Although the patient's age, sex, and the duration of the disease were not related to hearing loss, there was a significant correlation between a negative pathergy test and hearing loss in patients with Behçet syndrome. CONCLUSION: We should consider audiovestibular involvement in Behçet syndrome as a common finding.