scholarly journals Detailed Clinical Features of Deafness Caused by a Claudin-14 Variant

2019 ◽  
Vol 20 (18) ◽  
pp. 4579 ◽  
Author(s):  
Kitano ◽  
Kitajiri ◽  
Nishio ◽  
Usami
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Cochlear Implantation ◽  
Vestibular Function ◽  
Sound Field ◽  
Speech Discrimination ◽  
Epithelial Barrier Function ◽  
Pathogenic Variants ◽  
Novel Variant ◽  
Claudin 14

Tight junctions are cellular junctions that play a major role in the epithelial barrier function. In the inner ear, claudins, occludin, tricellulin, and angulins form the bicellular or tricellular binding of membrane proteins. In these, one type of claudin gene, CLDN14, was reported to be responsible for human hereditary hearing loss, DFNB29. Until now, nine pathogenic variants have been reported, and most phenotypic features remain unclear. In the present study, genetic screening for 68 previously reported deafness causative genes was carried out to identify CLDN14 variants in a large series of Japanese hearing loss patients, and to clarify the prevalence and clinical characteristics of DFNB29 in the Japanese population. One patient had a homozygous novel variant (c.241C>T: p.Arg81Cys) (0.04%: 1/2549). The patient showed progressive bilateral hearing loss, with post-lingual onset. Pure-tone audiograms indicated a high-frequency hearing loss type, and the deterioration gradually spread to other frequencies. The patient showed normal vestibular function. Cochlear implantation improved the patient’s sound field threshold levels, but not speech discrimination scores. This report indicated that claudin-14 is essential for maintaining the inner ear environment and suggested the possible phenotypic expansion of DFNB29. This is the first report of a patient with a tight junction variant receiving a cochlear implantation.

Cochlear Implantation in Autoimmune Inner Ear Disease

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P53-P53 ◽  
Author(s):  
Katrina R Stidham ◽  
Joseph B Roberson
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Immunosuppressive Therapy ◽  
Cochlear Implantation ◽  
Hearing Aid ◽  
Speech Discrimination ◽  
Inner Ear Disease ◽  
Potential Risks ◽  
The Impact ◽  
Autoimmune Inner Ear Disease

Objective 1) Evaluate the success of cochlear implantation (CI) in patients with autoimmune inner ear disease (AIED). 2) Discuss the impact of CI on consideration of immunosuppressive therapy for patients with fluctuating hearing loss due to AIED. Methods Retrospective chart review was conducted of patients undergoing CI with diagnosis of AIED between 6/02 and 6/07. Patients’ autoimmune and immunotherapy treatment history was explored. Non-operative ear hearing thresholds and speech discrimination scores (SDS) were documented pre- and postoperatively. Objective and subjective implant success in setting of fluctuating hearing in non-implant ear was evaluated. Results Four patients with AIED, aged 5–55, underwent CI. Two had isolated otologic symptoms and 2 had other systemic autoimmune diagnoses. All had been previously treated with steroids. Three had received other immunosuppressive therapy. One declined other treatment due to potential risks. At the time of implantation, 3 patients had functional hearing in the non-implant ear and received benefit from a hearing aid. Each continued to have usable hearing, with fluctuating improvements post-implant at times to much better SDS than would normally meet candidacy requirements for CI. All patients found the implant provided better hearing than the hearing-aid ear. Conclusions CI is a viable option for patients with AIED. Implanting a profoundly deafened ear where opposite ear has fluctuating but usable hearing does not negatively impact outcomes. With the success of CI for AIED, the potential risks of long-term immunosuppressive therapy may not warrant its use in patients with isolated hearing loss symptoms.

Modification of Speech Discrimination in Patients with Binaural Asymmetrical Hearing Loss

1971 ◽  
Vol 36 (2) ◽  
pp. 208-212 ◽  
Author(s):  
Herbert J. Arkebauer ◽  
George T. Mencher ◽  
Carol McCall
Keyword(s):  
Hearing Loss ◽  
Sound Field ◽  
Combined Effect ◽  
Speech Signals ◽  
Speech Discrimination ◽  
The Difference ◽  
Better Than

Ten patients with bilateral asymmetrical hearing losses were tested for differences in speech discrimination scores under the following listening conditions: poorer ear under earphone; better ear under earphone; sound field, ears unoccluded; and sound field, poorer ear occluded. A patient manifesting a bilateral asymmetrical hearing loss may not be able to either separate or integrate two speech signals; however, occlusion of the poorer ear may be an advantageous means of obtaining maximum speech discrimination. Examination of the speech discrimination scores indicates the existence of detrimental interaction between ears exhibiting bilateral asymmetrical hearing loss. These findings also indicate that when the difference between ears is greater, speech discrimination is better than when asymmetry approximates symmetry. Apparently, the greater the impairment in the better ear, the greater the results to be gained by occluding the poorer ear. These findings were interpreted as being relevant in determining candidacy for binaural amplification. Such candidacy should be determined on the basis of speech discrimination scores obtained from each ear independently, and the combined effect of both aids.

scholarly journals Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiuhua Chao ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Jianfen Luo ◽  
Ruijie Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Whole Exome ◽  
Novel Variant ◽  
Genetic Features ◽  
The Right

Aims. This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods. A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results. A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion. A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

scholarly journals Characterization of a novel variant in the HR1 domain of MFN2 in a patient with ataxia, optic atrophy and sensorineural hearing loss

2021 ◽  
Author(s):  
Govinda Sharma ◽  
Rasha Saubouny ◽  
Matthew M Joel ◽  
Kristina Martens ◽  
Davide Martino ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cerebellar Ataxia ◽  
Optic Atrophy ◽  
Cerebellar Atrophy ◽  
Lipid Transfer ◽  
Motor Weakness ◽  
Charcot Marie Tooth Disease ◽  
Pathogenic Variants ◽  
Novel Variant

AbstractPathogenic variants in MFN2 cause Charcot-Marie-Tooth disease (CMT) type 2A (CMT2A) and are the leading cause of the axonal subtypes of CMT. CMT2A is characterized by predominantly distal motor weakness and muscle atrophy, with highly variable severity and onset age. Notably, some MFN2 variants can also lead to other phenotypes such as optic atrophy, hearing loss and lipodystrophy. Despite the clear link between MFN2 and CMT2A, our mechanistic understanding of how dysfunction of the MFN2 protein causes human disease pathologies remains incomplete. This lack of understanding is due in part to the multiple cellular roles of MFN2. Though initially characterized for its role in mediating mitochondrial fusion, MFN2 also plays important roles in mediating interactions between mitochondria and other organelles, such as the endoplasmic reticulum and lipid droplets. Additionally, MFN2 is also important for mitochondrial transport, mitochondrial autophagy, and has even been implicated in lipid transfer. Though over 100 pathogenic MFN2 variants have been described to date, only a few have been characterized functionally, and even then, often only for one or two functions. Here, we describe a novel homozygous MFN2 variant, D414V, in a patient presenting with cerebellar ataxia, deafness, blindness, and diffuse cerebral and cerebellar atrophy. Characterization of patient fibroblasts reveals phenotypes consistent with impaired MFN2 functions and expands the phenotypic presentation of MFN2 variants to include cerebellar ataxia.

The audiovestibular profile of Brown-Vialetto-Van Laere syndrome

2021 ◽  
Vol 135 (11) ◽  
pp. 1000-1009
Author(s):  
R Omar ◽  
K Rajput ◽  
T Sirimanna ◽  
S Rajput ◽  
W Pagarkar
Keyword(s):  
Hearing Loss ◽  
Characteristic Feature ◽  
Motor Function ◽  
Cochlear Implantation ◽  
Cranial Nerve ◽  
Vestibular Function ◽  
Auditory Neuropathy ◽  
Spectrum Disorder ◽  
Significant Heterogeneity ◽  
Auditory Neuropathy Spectrum Disorder

AbstractBackgroundBrown-Vialetto-Van Laere syndrome, a rare disorder associated with motor, sensory and cranial nerve neuropathy, is caused by mutations in riboflavin transporter genes SLC52A2 and SLC52A3. Hearing loss is a characteristic feature of Brown-Vialetto-Van Laere syndrome and has been shown in recent studies to be characterised by auditory neuropathy spectrum disorder.MethodThis study reports the detailed audiovestibular profiles of four cases of Brown-Vialetto-Van Laere syndrome with SLC52A2 and SLC52A3 mutations. All of these patients had auditory neuropathy spectrum disorder.ResultsThere was significant heterogeneity in vestibular function and in the benefit gained from cochlear implantation. The audiological response to riboflavin therapy was also variable, in contrast to generalised improvement in motor function.ConclusionWe suggest that comprehensive testing of vestibular function should be conducted in Brown-Vialetto-Van Laere syndrome, in addition to serial behavioural audiometry as part of the systematic examination of the effects of riboflavin.

scholarly journals TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling

2021 ◽  
Vol 12 ◽  
Author(s):  
In Seok Moon ◽  
Andrew R. Grant ◽  
Varun Sagi ◽  
Heidi L. Rehm ◽  
Konstantina M. Stankovic
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Cochlear Implantation ◽  
Clinical Manifestations ◽  
Clinical Information ◽  
Hearing Rehabilitation ◽  
Novel Variants ◽  
Novel Variant ◽  
Number Variation ◽  
Syndromic Hearing Loss

Objective: To identify and report novel variants in the TMPRSS3 gene and their clinical manifestations related to hearing loss as well as intervention outcomes. This information will be helpful for genetic counseling and treatment planning for these patients.Methods: Literature review of previously reported TMPRSS3 variants was conducted. Reported variants and associated clinical information was compiled. Additionally, cohort data from 18 patients, and their families, with a positive result for TMPRSS3-associated hearing loss were analyzed. Genetic testing included sequencing and copy number variation (CNV) analysis of TMPRSS3 and the Laboratory for Molecular Medicine’s OtoGenome-v1, -v2, or -v3 panels. Clinical data regarding patient hearing rehabilitation was interpreted along with their genetic testing results and in the context of previously reported cochlear implant outcomes in individuals with TMPRSS3 variants.Results: There have been 87 previously reported TMPRSS3 variants associated with non-syndromic hearing loss in more than 20 ancestral groups worldwide. Here we report occurrences of known variants as well as one novel variant: deletion of Exons 1–5 and 13 identified from our cohort of 18 patients. The hearing impairment in many of these families was consistent with that of previously reported patients with TMPRSS3 variants (i.e., typical down-sloping audiogram). Four patients from our cohort underwent cochlear implantation.Conclusion: Bi-allelic variants of TMPRSS3 are associated with down-sloping hearing loss regardless of ancestry. The outcome following cochlear implantation in patients with variants of TMPRSS3 is excellent. Therefore, cochlear implantation is strongly recommended for hearing rehabilitation in these patients.

scholarly journals Vestibular Function After Cochlear Implantation in Partial Deafness Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Magdalena Sosna-Duranowska ◽  
Grazyna Tacikowska ◽  
Elzbieta Gos ◽  
Anna Krupa ◽  
Piotr Henryk Skarzynski ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Low Frequency ◽  
Vestibular Function ◽  
Hearing Preservation ◽  
Caloric Test ◽  
Profound Hearing Loss ◽  
Single Sided Deafness ◽  
Caloric Response ◽  
Vestibular Damage

Introduction: Cochlear implantation is a fully accepted method of treating individuals with profound hearing loss. Since the indications for cochlear implantation have broadened and include patients with low-frequency residual hearing, single-sided deafness, or an already implanted ear (meaning bilateral cochlear implantation), the emphasis now needs to be on vestibular protection.Materials and Methods: The research group was made up of 107 patients operated on in the otorhinolaryngosurgery department: 59 females and 48 males, aged 10.4–80.2 years (M = 44.4; SD = 18.4) with hearing loss lasting from 1.4 to 56 years (M = 22.7; SD = 13.5). The patients underwent cVEMP, oVEMP, a caloric test, and vHIT assessment preoperatively, and, postoperatively, cVEMP and oVEMP at 1–3 months and a caloric test and vHIT at 4–6 months.Results: After cochlear implantation, there was postoperative loss of cVEMP in 19.2% of the patients, oVEMP in 17.4%, reduction of caloric response in 11.6%, and postoperative destruction of the lateral, anterior, and posterior semicircular canal as measured with vHIT in 7.1, 3.9, and 4% respectively.Conclusions: Hearing preservation techniques in cochlear implantation are connected with vestibular protection, but the risk of vestibular damage in never totally eliminated. The vestibular preservation is associated with hearing preservation and the relation is statistically significant. Informed consent for cochlear implantation must include information about possible vestibular damage. Since the risk of vestibular damage is appreciable, preoperative otoneurological diagnostics need to be conducted in the following situations: qualification for a second implant, after otosurgery (especially if the opposite ear is to be implanted), having a history of vestibular complaints, and when there are no strict audiological or anatomical indications on which side to operate.

scholarly journals Characterization of a novel variant in the HR1 domain of MFN2 in a patient with ataxia, optic atrophy and sensorineural hearing loss

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 606
Author(s):  
Govinda Sharma ◽  
Rasha Sabouny ◽  
Matthew Joel ◽  
Kristina Martens ◽  
Davide Martino ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cerebellar Ataxia ◽  
Optic Atrophy ◽  
Lipid Droplets ◽  
Cerebellar Atrophy ◽  
Mitochondrial Fusion ◽  
Lipid Transfer ◽  
Mtdna Copy Number ◽  
Pathogenic Variants ◽  
Novel Variant

Background: Pathogenic variants in MFN2 cause Charcot-Marie-Tooth disease (CMT) type 2A (CMT2A) and are the leading cause of the axonal subtypes of CMT. CMT2A is characterized by predominantly distal motor weakness and muscle atrophy, with highly variable severity and onset age. Notably, some MFN2 variants can also lead to other phenotypes such as optic atrophy, hearing loss and lipodystrophy. Despite the clear link between MFN2 and CMT2A, our mechanistic understanding of how dysfunction of the MFN2 protein causes human disease pathologies remains incomplete. This lack of understanding is due in part to the multiple cellular roles of MFN2. Though initially characterized for its role in mediating mitochondrial fusion, MFN2 also plays important roles in mediating interactions between mitochondria and other organelles, such as the endoplasmic reticulum and lipid droplets. Additionally, MFN2 is also important for mitochondrial transport, mitochondrial autophagy, and has even been implicated in lipid transfer. Though over 100 pathogenic MFN2 variants have been described to date, only a few have been characterized functionally, and even then, often only for one or two functions. Method: Several MFN2-mediated functions were characterized in fibroblast cells from a patient presenting with cerebellar ataxia, deafness, blindness, and diffuse cerebral and cerebellar atrophy, who harbours a novel homozygous MFN2 variant, D414V, which is found in a region of the HR1 domain of MFN2 where few pathogenic variants occur. Results: We found evidence for impairment of several MFN2-mediated functions. Consistent with reduced mitochondrial fusion, patient fibroblasts exhibited more fragmented mitochondrial networks and had reduced mtDNA copy number. Additionally, patient fibroblasts had reduced oxygen consumption, fewer mitochondrial-ER contacts, and altered lipid droplets that displayed an unusual perinuclear distribution. Conclusion: Overall, this work characterizes D414V as a novel variant in MFN2 and expands the phenotypic presentation of MFN2 variants to include cerebellar ataxia.

Vestibular function in families with inherited autosomal dominant hearing loss

2008 ◽  
Vol 18 (1) ◽  
pp. 51-58
Author(s):  
Valerie A. Street ◽  
Jeremy C. Kallman ◽  
Paul D. Strombom ◽  
Naomi F. Bramhall ◽  
James O. Phillips
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Autosomal Dominant ◽  
Vestibular Function ◽  
Vestibular Dysfunction ◽  
Self Report ◽  
Vestibular Hypofunction ◽  
Mount Kilimanjaro ◽  
Vestibular Symptoms ◽  
Balance Problems

The inner ear contains the developmentally related cochlea and peripheral vestibular labyrinth. Given the similar physiology between these two organs, hearing loss and vestibular dysfunction may be expected to occur simultaneously in individuals segregating mutations in inner ear genes. Twenty-two different genes have been discovered that when mutated lead to non-syndromic autosomal dominant hearing loss. A review of the literature indicates that families segregating mutations in 13 of these 22 genes have undergone formal clinical vestibular testing. Formal assessment revealed vestibular dysfunction in families with mutations in ten of these 13 genes. Remarkably, only families with mutations in the COCH and MYO7A genes self-report considerable vestibular challenges. Families segregating mutations in the other eight genes do not self-report significant balance problems and appear to compensate well in everyday life for vestibular deficits discovered during formal clinical vestibular assessment. An example of a family (referred to as the HL1 family) with progressive hearing loss and clinically-detected vestibular hypofunction that does not report vestibular symptoms is described in this review. Notably, one member of the HL1 family with clinically-detected vestibular hypofunction reached the summit of Mount Kilimanjaro.

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