Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all ...previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) >0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.
To assess the role of serotonin transporter gene (SLC6A4) polymorphism in tinnitus.
Fifty-four consecutive patients experiencing subjective tinnitus and 174 healthy controls were allocated for the ...study. Psychoacoustic parameters of tinnitus were measured. Beck Depression Inventory was used to assess the depression level of the patients. Tinnitus Handicap Inventory was used to assess the severity of tinnitus. A visual analog scale was designed to measure the impact of tinnitus on quality of life of the patients. The 44-bp insertion-deletion in the promoter region (5-HTTLPR) and 17-bp variable number tandem repeats in the second intron of the serotonin transporter gene were assessed.
No difference was found between the genotypes and allele frequencies of the patients and controls regarding variable number tandem repeats and 5-HTTLPR polymorphisms (p > 0.05). There was no association between the psychoacoustic parameters of tinnitus and SLC6A4 polymorphism (p > 0.05). There was a significant association between the 5-HTTLPR polymorphism and scores from the visual analog scale of the patients (p < 0.05).
Generation of tinnitus signal is not associated with SLC6A4 polymorphism and possibly with serotonergic mechanisms. However, the "ll" genotype variant of the SLC6A4 polymorphic promoter region seems associated with the limbic and autonomic nervous system symptoms of the patients with tinnitus. Therefore, serotonergic mechanisms may help explain the neurophysiological model of tinnitus, and serotonin replacement or serotonin reuptake inhibitors may increase the success rate of tinnitus treatment modalities based on the neurophysiologic model of tinnitus.
Abstract Objective To analyze the association of GJB2 gene mutations with cochlear implant performance in children. Methods Sixty-five consecutive children who underwent cochlear implantation due to ...congenital profound senseurineural hearing between 2006 and 2008 were included in the study. In children, GJB2 gene mutation analysis was performed. Their auditory performance was assessed using MAIS, MUSS and LittlEARS tests. Results Twenty-two of sixty-five patients GJB2 mutations, and 35delG was the most frequent mutation. No significant difference was found between the auditory performance of mutation positive and negative children after one year follow up ( p > 0.05). Conclusion GJB2 gene mutations do not impact on the outcome of cochlear implantation.
Research on hereditary hearing impairment has had several boosts to identify deafness-causing genes. The number of studies regarding the diagnosis and treatment modalities of hereditary hearing ...impairment is enormous and increasing; however, little or no research has been conducted for evaluating the development of scientific output and trends in the field. Here, we provide a comprehensive overview of centers that focus their research on hereditary hearing impairment and their scientific output.
Bibliometric analysis of the publications related to hereditary hearing impairment published between 1980 and 2019 were used in this study, which were also indexed in Web of Science database.
The highest number of scientific articles on hereditary hearing impairment came from the United States, and it was also the most cited country. The University of Iowa is a leading center in the domain of hereditary hearing impairment in the world over the last 40 years. Fudan University, Central South University, and Harvard Medical School are also institutions that have had a focus on hereditary hearing impairment.
There is a progressive increase in scientific papers on hereditary hearing impairment over the last 40 years that we have found in our bibliometric study. We identified key centers in the scientific research on hereditary hearing impairment in the world and also key journals that focus on hereditary hearing impairment. This information can facilitate new researchers in this field to seek collaboration with experienced partners, better synthesize the orientation and boundaries of the subject, and find target journals. Ultimately, we provided a certain benchmark value for key centers that perhaps should have a more prominent role in constructing experimental research or even clinical guidelines.
An overview of hereditary hearing loss Bayazit, Yildirim A; Yilmaz, Metin
O.R.L. Journal for oto-rhino-laryngology and its related specialties,
03/2006, Letnik:
68, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Understanding the genetic basis of hearing loss is important because almost 50% of profound hearing loss are caused by genetic factors and more than 120 independent genes have been identified. In ...this review, after a brief explanation of some genetic terms (allele, heterozygosis, homozygosis, polymorphism, genotype and phenotype), classification of genetic hearing loss (syndromic versus nonsyndromic, and recessive dominant, X-linked and mitochondrial) was performed. Some of the most common syndromes (Usher, Pendred, Jervell and Lange-Nielsen, Waardenburg, branchio-oto-renal, Stickler, Treacher Collins and Alport syndromes, biotinidase deficiency and Norrie disease) causing genetic hearing loss were also explained briefly. The genes involved in hearing loss and genetic heterogeneity were presented.
To present the results of our experience with labyrinthotomy or vestibulotomy in cases where the oval window is blocked by the facial nerve and in the presence of bilateral congenital agenesis of the ...oval window, respectively.
Retrospective analysis of the records of the patients operated in two different centers.
Between 2007 and 2012, 5 ears of 4 patients who were operated on in two different clinics with a presumptive diagnosis of otosclerosis were included in the study. There were 3 female patients and 1 male. The ages ranged from 10 to 26 (mean 19 years). All patients had unilateral conductive hearing loss except 1 (10-year-old girl or patient 1). Pure tone averages were calculated at the frequencies 0.5, 1, 2 and 4 kHz both pre- and postoperatively according to the Committee on Hearing and Equilibrium 1995 Guidelines for the Evaluation of Results of Treatment of Conductive Hearing Loss. All patients underwent a middle ear exploration and postoperatively the initial audiological examination was performed after 6 months.
Retrospective analysis revealed that vestibulotomy or labyrinthotomy was performed in 5 ears of 4 patients. Postoperative dizziness was encountered in 2 patients who had vestibulotomy due to oval window agenesis, which ceased spontaneously at 1 month postoperatively. The perioperative period was otherwise uneventful. None of the patients had sensorineural hearing loss or deterioration of hearing. There was a significant improvement in hearing after the operation. A 28-dB improvement in the mean air conduction pure tone thresholds was achieved.
Vestibulotomy and labyrinthotomy are safe and effective procedures in terms of hearing restoration, which can be applied in cases of congenital agenesis of the oval window or obstruction of the oval window by the facial nerve.
To assess vestibular evoked myogenic potentials in patients with fibromyalgia syndrome.
Twenty-four patients with fibromyalgia syndrome (two men and 22 women) and 21 female controls were included in ...the study. All patients underwent vestibular evoked myogenic potential testing.
Statistical comparison of fibromyalgia patients with control subjects showed a significant difference with respect to n23 latencies and interpeak latencies (p < 0.05). There was no significant difference in p13 latencies, nor in p13 amplitudes, n23 amplitudes or interpeak amplitudes (p > 0.05).
Although patients with fibromyalgia syndrome generally have subjective neurotological symptoms, clinical and laboratory assessments usually fail to detect any objective abnormality. However, it is possible to detect abnormalities on vestibular evoked myogenic potential testing in such patients, indicating dysfunction in the vestibulospinal pathway, possibly in the saccule. Elongation of the n23 latency and of the interpeak latency of waves p13-n23, during vestibular evoked myogenic potential testing, may be a useful, objective indicator demonstrating neurotological involvement in fibromyalgia syndrome patients. Future research investigating the mechanisms of this latency elongation may help increase understanding of the pathogenesis of fibromyalgia syndrome.
We aimed to present the complications of auditory brain stem implantations (ABI) in pediatric patients which were performed via retrosigmoid approach.
Between March 2007 and February 2010, five ...prelingually deaf children underwent ABI (Medel device) operation via retrosigmoid approach. All children had severe cochlear malformations. The ages ranged from 20 months to 5 years. The perioperative complications encountered in 2 patients were evaluated retrospectively.
No intraoperative complication was observed in the patients. Cerebrospinal fluid (CSF) leakage was the most common postoperative complication that was seen in 2 patients. The CSF leak triggered a cascade of comorbidities, and elongated the hospitalization.
Pediatric ABI surgery can lead to morbidity. The CSF leak is the most common complication encountered in retrosigmoid approach. The other complications usually result from long-term hospital stay during treatment period of the CSF leak. Therefore, every attempt must be made to prevent occurrence of CSF leaks in pediatric ABI operations.
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