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Molecular Genetics and Genomics : MGG Aug 2019Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only...
Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only mutations in a single gene, SERPINF1, were previously published in patients with familial otosclerosis. To unravel the contribution of genetic variation in this gene to otosclerosis, this gene was re-sequenced in a large population of otosclerosis patients and controls. Resequencing of the 5' and 3' UTRs, coding regions, and exon-intron boundaries of SERPINF1 was performed in 1604 unrelated otosclerosis patients and 1538 unscreened controls, and in 62 large otosclerosis families. Our study showed no enrichment of rare variants, stratified by type, in SERPINF1 in patients versus controls. Furthermore, the c.392C > A (p.Ala131Asp) variant, previously reported as pathogenic, was identified in three patients and four controls, not replicating its pathogenic nature. We could also not find evidence for a pathogenic role in otosclerosis for 5' UTR variants in the SERPINF1-012 transcript (ENST00000573763), described as the major transcript in human stapes. Furthermore, no rare variants were identified in the otosclerosis families. This study does not support a pathogenic role for variants in SERPINF1 as a cause of otosclerosis. Therefore, the etiology of the disease remains largely unknown and will undoubtedly be the focus of future studies.
Topics: 3' Untranslated Regions; 5' Untranslated Regions; Case-Control Studies; Eye Proteins; Female; Humans; Male; Nerve Growth Factors; Otosclerosis; Pedigree; Sequence Analysis, DNA; Serpins
PubMed: 30968248
DOI: 10.1007/s00438-019-01558-8 -
The Annals of Otology, Rhinology, and... Apr 2024To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the...
OBJECTIVE
To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis.
METHODS
Archival celloidin formalin-fixed 20-micron thick histologic sections from 7 patients diagnosed with otosclerosis were studied and compared to controls. Sections in the mid-modiolar region were immunoreacted with rabbit polyclonal antibodies against nidogen-1, β2-laminin, collagen-IX, BSP, and monoclonal antibodies against TGF β-1 and ubiquitin. Digital images were acquired using a high-resolution light and laser confocal microscope.
RESULTS
Nidogen-1, BSP, and collagen-IX were expressed in the otospongiotic regions, and to lesser extent, in the otosclerotic regions, the latter previously believed to be inactive. β2-laminin and ubiquitin were uniformly expressed in both otospongiotic and otosclerotic regions. There was a basal level of expression of all of these markers in the normal hearing and sensorineural hearing loss specimens utilized as control. TGF β -1, however, though present in the otosclerosis bones, was absent in the normal hearing and sensorineural hearing loss controls.
CONCLUSIONS
Our results propose that the activity and function of TGF-1 may play a key role in the development and pathogenesis of otosclerosis. Further studies utilizing a higher number of temporal bone specimens will be helpful for future analysis and to help decipher its role as a potential target in therapeutic interventions.
Topics: Humans; Rabbits; Animals; Otosclerosis; Cochlea; Hearing Loss, Sensorineural; Collagen; Laminin; Ubiquitins
PubMed: 38197255
DOI: 10.1177/00034894231225134 -
Auris, Nasus, Larynx Aug 2016Otosclerosis and osteoporosis are metabolic bone diseases. In this paper, we investigated presence of osteoporosis with bone mineral density test in patients who had...
OBJECTIVE
Otosclerosis and osteoporosis are metabolic bone diseases. In this paper, we investigated presence of osteoporosis with bone mineral density test in patients who had surgery for otosclerosis.
METHODS
We included 27 patients who had conductive hearing loss and diagnosed with otosclerosis during an exploratory tympanotomy, and 30 healthy controls into this study. Bone mineral densitometry test was used for analysis of osteoporosis. T-scores of the patients and the controls obtained from L1-L4 vertebrae and femur neck were compared. In addition, the relations of duration of the disease, air and bone conduction thresholds, and air-bone gap in the operated ear with 25(OH)D3 levels, T-scores obtained from L1-L4 vertebrae and femur neck were investigated in the otosclerosis group.
RESULTS
T-score obtained from L1-L4 region was -1.14±1.05 in the otosclerosis group, and was -0.56±1.10 in the control group; the difference was statistically significant (p=0.045). The T-scores obtained from the femur neck were -0.59±0.82 and 0.03±0.74 in the otosclerosis and the control groups respectively, with a statistically significant difference in between (p=0.004). As the air and bone conduction thresholds and the air-bone gaps of the patients with otosclerosis increased, 25(OH)D3 levels and T-scores decreased, but the differences were not statistically significant.
CONCLUSION
The relation between otosclerosis and osteoporosis was shown with bone mineral density test in our study. T-scores of the otosclerosis patients were found smaller than the normal population.
Topics: Absorptiometry, Photon; Adult; Audiometry, Pure-Tone; Bone Conduction; Bone Density; Calcifediol; Case-Control Studies; Female; Femur Neck; Hearing Loss, Conductive; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Otosclerosis; Retrospective Studies; Stapes Surgery
PubMed: 26656733
DOI: 10.1016/j.anl.2015.11.001 -
Otology & Neurotology : Official... Jan 2016To evaluate the diagnostic value of computed tomography (CT) in detecting otosclerosis in patients with conductive hearing loss and a clinical suspicion of otosclerosis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the diagnostic value of computed tomography (CT) in detecting otosclerosis in patients with conductive hearing loss and a clinical suspicion of otosclerosis.
DATA SOURCES
PubMed, Embase, and the Cochrane Library.
STUDY SELECTION
A systematic search was conducted. Studies reporting original study data were included.
DATA EXTRACTION
Relevance and risk of bias of the selected articles were assessed. Studies with low relevance, high risk of bias, or both were excluded. Prevalences, sensitivities, specificities, and post-test probabilities were extracted from the included articles.
DATA SYNTHESIS
Seven studies characterized by a moderate to high relevance and moderate to low risk of bias were included for data extraction. The prevalence of otosclerosis was high (up to 100%) in the majority of the included studies. In those studies with a high prevalence of disease, both positive and negative post-test probabilities were (relatively) high: 99% and between 51% and 67% respectively. In one study with a low prevalence of disease (9%), both positive and negative post-test probabilities were low (23% and 3% respectively). Overall, reported sensitivities ranged between 60% and 95%.
CONCLUSION
Preoperative CT has little to add in establishing otosclerosis and may not be necessary to confirm the diagnosis. We would recommend reserving CT for those patients with suspected additional abnormalities, for specific preoperative planning, or out of legal necessity.
Topics: Hearing Loss, Conductive; Humans; Otosclerosis; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 26649602
DOI: 10.1097/MAO.0000000000000924 -
Acta Oto-laryngologica Oct 2021The success rate of stapedotomy in otosclerosis patients with cochlea involvement was unknown.
BACKGROUND
The success rate of stapedotomy in otosclerosis patients with cochlea involvement was unknown.
AIMS/OBJECTIVES
To determine the difference of surgical outcomes and symptomatology in otosclerosis patients with or without cochlea involvement on CT.
MATERIAL AND METHODS
79 otosclerosis patients were included and grouped by HRCT, including cochlear-involved otosclerosis (C-group) or non-cochlear-involved otosclerosis (NC-group, control group). Patients were defined as NC-group in the presence of normal or solely fenestral involvement, or C-group if the hypodensities involve other parts of the labyrinthine bone Patients in the control group were collected at a 2:1 ratio to the C-group with similar follow-up times. Detailed complaints and surgical outcomes were compared between these groups.
RESULTS
Chief complaints were similar in the C-group and NC-group. Although postoperative AC, BC, and ABG decreased significantly in both groups, the success rate was significantly higher in C-group regarding the postoperative ABG ≤10 dB. Furthermore, diffuse lesions may indicate a more severe disease and a poorer prognosis.
CONCLUSIONS AND SIGNIFICANCE
Stapedotomy was effective for clinical otosclerosis. The surgical outcome was inferior favorable for cochlea involvement patients, especially for cases with widely involvement. There was no difference in chief complaints among patients with different CT degree of otosclerosis.
Topics: Adult; Auditory Threshold; Bone Conduction; Case-Control Studies; Cochlea; Female; Hearing Loss; Humans; Male; Otosclerosis; Retrospective Studies; Stapes Surgery; Tomography, X-Ray Computed
PubMed: 34633897
DOI: 10.1080/00016489.2021.1980225 -
AJNR. American Journal of Neuroradiology Nov 2017Focal low-attenuation outpouching or diverticulum at the anterolateral internal auditory canal is an uncommon finding on CT of the temporal bone. This finding has been...
BACKGROUND AND PURPOSE
Focal low-attenuation outpouching or diverticulum at the anterolateral internal auditory canal is an uncommon finding on CT of the temporal bone. This finding has been described as cavitary otosclerosis in small case reports and histology series. The purpose of this study was to establish the prevalence of internal auditory canal diverticulum and its association with classic imaging findings of otosclerosis and/or hearing loss.
MATERIALS AND METHODS
Temporal bone CT scans of 807 patients, obtained between January 2013 and January 2016, were retrospectively reviewed to identify internal auditory canal diverticula and/or classic imaging findings of otosclerosis. Clinical evaluations for hearing loss were reviewed for patients with internal auditory canal diverticula and/or otosclerosis.
RESULTS
Internal auditory canal diverticula were found in 43 patients (5%); classic otosclerosis, in 39 patients (5%); and both findings, in 7 patients (1%). Most temporal bones with only findings of internal auditory canal diverticula (91%) demonstrated hearing loss, with 63% of this group demonstrating sensorineural hearing loss. The hearing loss classification distribution was significantly different ( < .01) from that in the classic otosclerosis group and in the group with both diverticula and otosclerosis.
CONCLUSIONS
Internal auditory canal diverticula are not uncommon on CT examinations of the temporal bone and most commonly occur without classic imaging findings of otosclerosis. These lesions are associated with sensorineural hearing loss, and referral for hearing evaluation may be appropriate when present.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Diverticulum; Female; Hearing Loss, Sensorineural; Humans; Labyrinth Diseases; Male; Middle Aged; Otosclerosis; Prevalence; Retrospective Studies; Tomography, X-Ray Computed; Young Adult
PubMed: 28982792
DOI: 10.3174/ajnr.A5399 -
Otology & Neurotology : Official... Jun 2022To systematically review the evidence for the use of bisphosphonate therapy in otosclerosis through clinically relevant outcomes.
OBJECTIVE
To systematically review the evidence for the use of bisphosphonate therapy in otosclerosis through clinically relevant outcomes.
DATABASES REVIEWED
MEDLINE, EMBASE, PubMed, and CINAHL databases were searched up to July 12, 2021.
METHODS
RCTs and cohort studies investigating the effect of bisphosphate therapy on adults or children diagnosed with otosclerosis were included. The risk of bias within trials was examined using the ROB2 tool for RCTs, and the ROBINS-I for non-RCTs.
RESULTS
Three studies reported over five publications were included in the systematic review. Data from one RCT at 6 months did not demonstrate any improvement nor deterioration in audiological outcomes in participants treated with Sodium Alendronate. Data from MRI in this group demonstrated improvements in the SI of the otosclerotic foci at the RAOW compared to participants taking placebo. In another RCT, improvements in audiological outcomes were seen at 12 and 24 months in individuals treated with Etidronate Sodium. Long-term data from a retrospective cohort study demonstrated stabilisation of hearing in individuals with otosclerosis and progressive SNHL.
CONCLUSION
There is insufficient evidence to recommend the routine use of bisphosphonates in otosclerosis patients at present. Long-term retrospective data has suggested a role for bisphosphonates in the subset of patients with deteriorating sensorineural hearing loss with the aim of hearing stabilisation. Adequately powered RCTs with long term follow up will be required to evaluate this further.
Topics: Adult; Child; Diphosphonates; Etidronic Acid; Hearing Loss, Sensorineural; Humans; Otosclerosis; Retrospective Studies; Sodium
PubMed: 35213475
DOI: 10.1097/MAO.0000000000003510 -
Medicinski Pregled 2015
Topics: Cochlear Implants; History, 20th Century; History, 21st Century; Humans; Otosclerosis; Serbia; Stapes Surgery
PubMed: 26234021
DOI: No ID Found -
BMC Medical Genetics Jun 2020Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss in adults and is characterized by an abnormal bone growth in the otic capsule.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss in adults and is characterized by an abnormal bone growth in the otic capsule. Alteration in the osteoprotegerin (OPG) expression has been suggested in the implication of OTSC pathogenesis.
METHODS
A case-control association study of rs2228568, rs7844539, rs3102734 and rs2073618 single nucleotide polymorphisms (SNPs) in the OPG gene was performed in a Tunisian-North African population composed of 183 unrelated OTSC patients and 177 healthy subjects. In addition, a multilocus association and a meta-analysis of existing studies were conducted.
RESULTS
Rs3102734 (p = 0.013) and rs2073618 (p = 0.007) were significantly associated with OTSC, which were predominantly detected in females after multiple corrections. Among the OPG studied SNPs, the haplotypes A-A-C-G (p = 0.0001) and A-A-C-C (p = 0.0004) were significantly associated with OTSC in females. Multilocus association revealed that the SNPs: rs2073618 in OPG, rs1800472 in TGFβ1, rs39335, rs39350 and rs39374 in RELN, and rs494252 in chromosome 11 showed significant OTSC-associated alleles in Tunisian individuals. In addition, meta-analysis of the rs2073618 SNP in Tunisian, Indian and Italian populations revealed evidence of an association with OTSC (OR of 0.826, 95% CI [0.691-0.987], p = 0.035).
CONCLUSIONS
Our findings suggest that rs3102734 and rs2073618 variants are associated with OTSC in North African ethnic Tunisian population. Meta-analysis of the rs2073618 in three different ethnic population groups indicated an association with OTSC.
Topics: Alleles; Case-Control Studies; Chromosome Mapping; Epistasis, Genetic; Female; Gene Frequency; Genetic Association Studies; Genetic Loci; Genetic Predisposition to Disease; Haplotypes; Humans; Linkage Disequilibrium; Male; Models, Biological; Odds Ratio; Osteoprotegerin; Otosclerosis; Polymorphism, Single Nucleotide; Reelin Protein
PubMed: 32493243
DOI: 10.1186/s12881-020-01036-8 -
Otology & Neurotology : Official... Jun 2024To evaluate the effectiveness of cochlear implantation (CI) in case of far advanced otosclerosis and to evaluate the value of using intraoperative otoendoscopy to...
OBJECTIVES
To evaluate the effectiveness of cochlear implantation (CI) in case of far advanced otosclerosis and to evaluate the value of using intraoperative otoendoscopy to facilitate the identification of the round window membrane and the scala tympani without the need to remove the posterior canal wall or to perform a subtotal petrosectomy.
STUDY DESIGN
Retrospective case-series study.
SETTING
Tertiary academic CI center.
PATIENTS AND METHODS
This study was conducted on patients with far advanced otosclerosis who underwent endoscopic-assisted CI between January 2010 and June 2020 at the same CI center. The minimum follow-up period was 2 years after surgery.
RESULTS
Fourteen patients were included in the study. Ten patients had undergone a previous stapedotomy. Electrode insertion in the scala tympani was successfully accomplished in all cases included in the study. There was a statistically significant improvement in pure-tone average and speech discrimination scores in all cases of the study group (p < 0.0001). There were no statistically significant differences in postoperative pure-tone average or speech discrimination scores between cases with and without cochlear ossification or between cases with and without a previous stapedotomy (p > 0.05).
CONCLUSION
Endoscopic-assisted CI is an effective option for hearing restoration in patients with far advanced otosclerosis. Otoendoscopy can facilitate visualization and access to the scala tympani without the need to remove the posterior canal wall or to perform a subtotal petrosectomy.
Topics: Humans; Otosclerosis; Male; Female; Retrospective Studies; Middle Aged; Cochlear Implantation; Endoscopy; Adult; Aged; Treatment Outcome
PubMed: 38728555
DOI: 10.1097/MAO.0000000000004192