Combination Of Hearing Loss Research Articles

Usher syndrome: Genetic diagnosis and current therapeutic approaches

Usher Syndrome (USH) is the most common deaf-blind syndrome, affecting approximately 1 in 6000 people in the deaf population. This genetic condition is characterized by a combination of hearing loss (HL), retinitis pigmentosa, and, in some cases, vestibular areflexia. Among the subtypes of USH, USH type 1 is considered the most severe form, presenting profound bilateral congenital deafness, vestibular areflexia, and early onset RP. USH type 2 is the most common form, exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies. Conversely, type 3 is the rarest, initially manifesting mild symptoms during childhood that become more prominent in the first decades of life. The dual impact of USH on both visual and auditory senses significantly impairs patients’ quality of life, restricting their daily activities and interactions with society. To date, 9 genes have been confirmed so far for USH: MYO7A , USH1C , CDH23 , PCDH15 , USH1G , USH2A , ADGRV1 , WHRN and CLRN1 . These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina, leading to functional loss. Although non-genetic methods can assist in patient triage and disease extension evaluation, genetic and molecular tests play a pivotal role in providing genetic counseling, enabling appropriate gene therapy, and facilitating timely cochlear implantation (CI). The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH. Regarding drug therapy, PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH. Simultaneously, CI has proven to be critical in the restoration of hearing. This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in guiding appropriate treatment strategies and improving patient prognosis.

USHER SYNDROME AND ITS GENETIC CHARACTERIZATION

Usher syndrome is defined as an autosomal recessive disorder which is caused by a mutation in any one of at least 10 genes resulting in a combination of hearing loss and visual impairment. The loss of hearing is caused by a defect in the inner ear, whereas degeneration of the retinal cells called retinitis pigmentosa (RP), results in loss of vision. Based on severity and age whensigns and symptoms appear, there are three clinical subtypes of Usher syndrome (characterized as Usher I, II, and III). People suffering from Usher I are deaf by birth and during the first decade of life, they begin to lose their vision. Balance difficulties are also exhibited by them. Patients with Usher II have hearing loss but they are not deaf by birth. They also lose their vision later on. They do not show problems with balance. People having Usher syndrome III lose their vision and hearing gradually but they are not born deaf; they may or may not show difficulties with balance. In this review, those mouse models for usher syndrome will be discussed in which homologue of humans was identified first and a model called, “mouse model” was based upon gene defects in the human beings.

Usher Syndrome Belongs to the Genetic Diseases Associated with Radiosensitivity: Influence of the ATM Protein Kinase.

Usher syndrome (USH) is a rare autosomal recessive disease characterized by the combination of hearing loss, visual impairment due to retinitis pigmentosa, and in some cases vestibular dysfunctions. Studies published in the 1980s reported that USH is associated with cellular radiosensitivity. However, the molecular basis of this particular phenotype has not yet been documented. The aim of this study was therefore to document the radiosensitivity of USH1—a subset of USH—by examining the radiation-induced nucleo-shuttling of ATM (RIANS), as well as the functionality of the repair and signaling pathways of the DNA double-strand breaks (DSBs) in three skin fibroblasts derived from USH1 patients. The clonogenic cell survival, the micronuclei, the nuclear foci formed by the phosphorylated forms of the X variant of the H2A histone (ɣH2AX), the phosphorylated forms of the ATM protein (pATM), and the meiotic recombination 11 nuclease (MRE11) were used as cellular and molecular endpoints. The interaction between the ATM and USH1 proteins was also examined by proximity ligation assay. The results showed that USH1 fibroblasts were associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired DSB recognition but normal DSB repair, likely caused by a delayed RIANS, suggesting a possible sequestration of ATM by some USH1 proteins overexpressed in the cytoplasm. To our knowledge, this report is the first radiobiological characterization of cells from USH1 patients at both molecular and cellular scales.

Применение регистрации стационарных слуховых потенциалов в свободном звуковом поле у слепоглухого ребенка

Deafblindness is a rare disease in which a person has a combination of hearing loss and vision loss, resulting in reduced access to both auditory and visual information. There are many reasons to occur of deafblindness: hereditary syndromes/disorders (CHARGE syndrome, Usher’s syndrome, Down’s syndrome), diseases that occurred before childbirth (cytomegalovirus, hydrocephalus, microcephaly), etc. The article presents a clinical case of an 11-year-old patient with a diagnosis of severe bilateral sensorineural hearing loss, condition after cochlear implantation on the right in 2012. Retinopathy of prematurity of the 5th degree, total retinal detachment with severe intraretinal proliferation. Infantile cerebral palsy. Hyperhomocysteinemia. Mitochondrial dysfunction. Casein intolerance. Persistent viral infection of Herpes Simplex Virus (HSV) type 6, Epstein–Barr virus (EBV). The authors showed a method for fitting the cochlear implant (CI) processor in a deaf-blind child by assessing the thresholds for perceiving sounds at different speech frequencies (500 Hz–4,000 Hz), which is the registration via Auditory Steady State Response (ASSR) to acoustic stimuli delivered through loudspeakers to an activated cochlear implant processor.

Genomic study of a large family with complex neurological phenotype including hearing loss, imbalance and action tremor

Neurological disorders are often associated with a variety of symptoms, which can result from the combined action of genetic variants. We conducted a whole-genome analysis of a previously unreported unique multigenerational Dutch-Canadian family with a complex phenotype presenting with a combination of hearing loss, balance issues or action tremor. Ten family members were available for genetic study. The hearing loss and balance problems are explained by a pathogenic p.P51S substitution in COCH, which is a known founder mutation in Dutch and Belgium families affected by non-syndromic progressive sensorineural hearing loss often accompanied by vestibular dysfunction. Notably, p.P51S did not co-segregate with action tremor in our and reported kindreds. In our family, all 5 patients with tremor were carriers of the extremely rare p.R247W substitution in MCM9 (minor allele frequency in European population is 0.00003), which belongs to the top 0.1% of deleterious variants in the human genome. The MCM9 locus has not been previously associated with action tremor and deserves further investigation in future functional and genetic studies of action tremor.

Cervical Nerve Projections to the Auditory Pathway in Tinnitus.

Cervical spinal nerves project to the auditory system and take part in the pathology of tinnitus. The intention of our research was to estimate the outcome of treatment of C6 and C7 to lessen tinnitus intensity and to find criteria for a long-term success. Subjects were 78 tinnitus patients who were treated with infiltration of the sixth and seventh cervical nerve. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. In a cohort of tinnitus patients, 18% had less tinnitus after treatment of C6 and C7. The majority of the patients announced a moderate easing of their tinnitus. At 2,5 months, half of the patients with a positive response still had benefit. The combination of hearing loss at 8 kHz and the highness of the intervertebral disc at C4-C5 forecasted a beneficial result of therapy of C6 and C7 with a longer period of relief. Treating afferent cervical nerves can lessen tinnitus. Therapy of C6 and C7 caused less tinnitus for 18% of the tinnitus patients. Especially patients with no hearing loss at 8 kHz and no disc degeneration at C4-C5 forecasted a beneficial result of therapy of C6 and C7 on tinnitus with a longer period of relief.

Efficacy and safety of deferiprone for the treatment of superficial siderosis: results from a long-term observational study.

Superficial siderosis (SS) of the central nervous system is a rare and heterogeneous condition due to deposition of hemosiderin on the surface of the brain and spinal cord. The usually progressive clinical course is characterized by a combination of hearing loss, cerebellar ataxia, and myelopathy. There is no known treatment for SS, but the iron chelator deferiprone (DFP) has been proposed as a potentially useful treatment. We present a long-term (average 3.7years) evaluation of four cases of SS treated with DFP (15mg/kg po bid). Treatment with DFP proved safe and well tolerated. Two out of the four subjects were unchanged while the other two presented a clinical improvement with reduction of postural instability and cerebellar signs. Blinded evaluation of magnetic resonance imaging (performed every 6months during follow-up) showed a reduction of the abnormal iron deposition for all patients. This long-term observational study suggests that DFP may be effective in the management of the neurological manifestations associated with iron accumulation in SS. CLINICALTRIALS. NTC00907283.

Transsphenoidal and infralabyrinthine approach of the petrous apex cholesterol granuloma.

Space-demanding or destructive changes in the petrous bone are often challenging differential diagnosis. Cholesterol granulomas of the petrous apex can clinically present in a combination of hearing loss, vertigo, tinnitus, chronic cephalgia, impairment of facial nerve function, neuralgic pain of the nervus trigeminus, or manifest diplopia by the nerve palsy of the nervus abducens. CT-morphologically cholesterol granulomas appear as soft-tissue density masses, which may display a discrete rim after intravenous administration of a contrast agent. The MRI, T1 as well as T2-weighted images show a strong signal in the area of the lesion. Depending on the individual anatomical conditions, the surgical access must be carefully chosen between transsphenoidal, transtemporal, infracochlear/-labyrinthine, or translabyrinthine. Here, we present the transsphenoidal and translabyrinthine access for the excision of cholesterol granulomas of the petrous apex. The different accesses are compared using a neuro-navigation-supported surgical technique with respect to its complications, drainage possibilities, outcomes, and recurrence of symptoms.

Insights on Impact of Missense SNPs of Human USH2A associated with Usher Syndrome II

Usher syndrome, also known as Hallgren syndrome, is an extremely rare genetic disorder caused by a mutation in any one of at least 11 genes resulting in a combination of hearing loss and visual impairment. It is a leading cause of deaf blindness and is at present incurable. Usher syndrome is classed into three subtypes according to onset and severity of symptoms. All three subtypes are caused by mutations in genes involved in the function of the inner ear and retina. Usher II are generally hard-of-hearing rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system. Usher syndrome type II occurs at least as frequently as type I, but because type II may be under diagnosed or more difficult to detect, it could be up to three times as common as type I. Usher syndrome type II may be caused by mutations in any of three different genes: USH2A, GPR98, and DFNB31. The protein encoded by the USH2A gene, usherin, is located in the supportive tissue in the inner ear and retina. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. In this study we investigate the most deleterious and disease associated SNPs in USH2A by using PolyPhen, SIFT, PANTHER, I-mutant 2.0, PhD-SNP, SNP&GO, Pmut, and Mutpred tools. The results showed mutation C759F and C536R in USH2A gene found to be most deleterious SNPs among the dataset. Our study will facilitate wet-lab researches to develop a potentdrug therapies against these USH2A mutant patients for Usher syndrome II treatment.

Using Cognitive Screening Tests in Audiology.

The population of the United States is aging. Those older adults are living longer than ever and have an increased desire for social participation. As a result, audiologists are likely to see an increased demand for service by older clients whose communication difficulty is caused by a combination of hearing loss and cognitive impairment. For these individuals, early detection of mild cognitive impairment is critical for providing timely medical intervention and social support. This tutorial provides information about cognition of older adults, mild cognitive impairment, and cognitive screening tests, with the purpose of assisting audiologists in identifying and appropriately referring potential cases of cognitive impairment. Topics addressed also include how to administer cognitive screening tests on individuals with hearing loss, how to use test results in audiology practice, and the potential of using cognitive screening tests for evaluating the benefit of clinical interventions. As health care professionals who serve the aging population, audiologists are likely to encounter cases of undiagnosed cognitive impairment. In order to provide timely referral for medical assistance as well as an optimized individual outcome of audiologic interventions, audiologists should be trained to recognize an abnormality in older clients' cognitive status.

Hearing loss in adults surviving pneumococcal meningitis is associated with otitis and pneumococcal serotype

We assessed the incidence of hearing loss and its relationship with clinical characteristics and pneumococcal serotypes in adults surviving pneumococcal meningitis. We analysed hearing loss in 531 adults surviving pneumococcal meningitis included in two prospective nationwide cohort studies performed from April 1998 through to October 2002 and March 2006 through to January 2009. Hearing loss was evaluated on admission and discharge for all patients. Severe hearing loss was assessed by pure tone average on audiology and corrected for age, or by the combination of hearing loss on discharge and a score on the Glasgow Outcome Scale below 5, which could not be explained by other neurological sequelae. A total of 531 episodes of pneumococcal meningitis with non-lethal outcome were included. Predisposing conditions for pneumococcal meningitis were present in the majority of patients (64%), most commonly otitis (36%). Hearing loss was present at discharge in 116 patients (22%) and was classified as mild in 53% and severe in 47%. Hearing loss was related to otitis (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.66–4.02; p < 0.001) and inversely related to serotype 23F infection (OR, 0.36; 95% CI, 0.13–0.98; p = 0.025), but not with parameters of disease severity or indicators of cerebrospinal fluid inflammation severity. Meningitis due to pneumococcal serotype 3 was associated with the highest rate of hearing loss. Hearing loss frequently complicates pneumococcal meningitis. Risk factors for hearing loss were infection with pneumococcal serotype 23F and otitis, but not disease severity. Otitis and resulting perilympathic inflammation contribute to meningitis-associated hearing loss.

Antiphospholipid antibodies in patients with sensorineural hearing loss

Sensorineural hearing loss can be associated with autoimmune diseases and the presence of antiphospholipid antibodies. Sixty patients (mean age 47 years, range 18-76 years) with sudden sensorineural hearing loss were studied with audiograms, stapedial thresholds, otoacoustic emissions, positional and caloric testing. The serologic testing included antibodies against phosphatidylserine and beta(2)-glycoprotein. Additionally, a group of 34 patients (mean age 65 years, range 31-81 years) with normal tension glaucoma was examined because in a previous study these patients were reported to have elevated concentrations of antiphospholipid antibodies with a coincidence of progressive sensorineural hearing loss. The baseline for antiphospholipid antibody levels was established in a control group of 40 healthy blood donors. In 12 of the 60 patients with sudden sensorineural hearing loss, levels of antiphospholipid antibodies were elevated. Antiphosphatidylserine IgM antibodies were significantly lower compared to controls and patients with the combination of hearing loss and normal tension glaucoma (Fisher's exact two-sided test, P < 0.01). Our data suggest that antibodies against beta2-glycoprotein seem to coincidence with an acute event, such as sudden sensorineural hearing loss, whereas antibodies against phosphatidylserine IgG are detectable in the prolonged sequel, such as in patients with progressive sensorineural hearing loss and normal tension glaucoma.

Acute cochlear disorders: the combination of hearing loss, recruitment, poor speech discrimination, and tinnitus.

The combination of hearing loss, recruitment, poor speech discrimination and tinnitus, which is characteristic of acute cochlear disorders, can be accounted for on the basis of a decoupling of hair cells from their drive system, the tectorial membrane. Decoupling may either be caused by a temporary reduction of ciliary stiffness (shown to occur during periods of noise-induced temporary threshold shifts) or by temporary and/or chronic ciliary pathology (demonstrated to exist in cases of antibiotic ototoxicity and in endolymphatic hydrops). Since ciliary coupling is elastic in nature, the decoupling is only partial. The hearing loss and the tinnitus are manifestations of the reduced coupling per se, the magnitude of the loss depending on the degree of decoupling and the number of hair cells involved. Recruitment and poor speech discrimination result from center-clipping of the signal waveform applied to an involved hair cell, the direct corollary of partial, ciliary decoupling.