scholarly journals Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 715 ◽  
Author(s):  
Sugiyama ◽  
Moteki ◽  
Kitajiri ◽  
Kitano ◽  
Nishio ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
Japanese Patients ◽  
Copy Number Variations ◽  
Clinical Feature ◽  
Single Nucleotide Variants ◽  
Characteristic Clinical Feature ◽  
Or Gene ◽  
Homozygous Deletions

The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified CNVs in 234 of 2262 (10.3%, 234/2262) patients with autosomal recessive hearing loss. Among the identified CNVs, OTOA gene-related CNVs were the second most frequent (0.6%, 14/2262). Among the 14 cases, 2 individuals carried OTOA homozygous deletions, 4 carried heterozygous deletions with single nucleotide variants (SNVs) in another allele. Additionally, 1 individual with homozygous SNVs in the OTOA gene was also identified. Finally, we identified 7 probands with OTOA-associated hearing loss, so that its prevalence in Japanese patients with autosomal recessive hearing loss was calculated to be 0.3% (7/2262). As novel clinical features identified in this study, the audiometric configurations of patients with OTOA-associated hearing loss were found to be mid-frequency. This is the first study focused on the detailed clinical features of hearing loss caused by this gene mutation and/or gene deletion.

scholarly journals Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 735 ◽  
Author(s):  
Karuna Maekawa ◽  
Shin-ya Nishio ◽  
Satoko Abe ◽  
Shin-ichi Goto ◽  
Yohei Honkura ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Features ◽  
Hair Cells ◽  
Autosomal Recessive ◽  
Haplotype Analysis ◽  
Genetic Factors ◽  
Hot Spot ◽  
Japanese Patients ◽  
Novel Variants ◽  
Accompanying Symptoms

Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.

scholarly journals Frequency of the STRC-CATSPER2 deletion in STRC-associated hearing loss patients

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shin-ya Nishio ◽  
Shin-ichi Usami
Keyword(s):  
Hearing Loss ◽  
Male Infertility ◽  
Genetic Counselling ◽  
Copy Number ◽  
Read Depth ◽  
Copy Number Variations ◽  
Genomic Region ◽  
High Prevalence ◽  
Homozygous Deletions ◽  
Next Generation Sequencing Ngs

AbstractThe STRC gene, located on chromosome 15q15.3, is one of the genetic causes of autosomal recessive mild-to-moderate sensorineural hearing loss. One of the unique characteristics of STRC-associated hearing loss is the high prevalence of long deletions or copy number variations observed on chromosome 15q15.3. Further, the deletion of chromosome 15q15.3 from STRC to CATSPER2 is also known to be a genetic cause of deafness infertility syndrome (DIS), which is associated with not only hearing loss but also male infertility, as CATSPER2 plays crucial roles in sperm motility. Thus, information regarding the deletion range for each patient is important to the provision of appropriate genetic counselling for hearing loss and male infertility. In the present study, we performed next-generation sequencing (NGS) analysis for 9956 Japanese hearing loss patients and analyzed copy number variations in the STRC gene based on NGS read depth data. In addition, we performed Multiplex Ligation-dependent Probe Amplification analysis to determine the deletion range including the PPIP5K1, CKMT1B, STRC and CATSPER2 genomic region to estimate the prevalence of the STRC-CATSPER deletion, which is causative for DIS among the STRC-associated hearing loss patients. As a result, we identified 276 cases with STRC-associated hearing loss. The prevalence of STRC-associated hearing loss in Japanese hearing loss patients was 2.77% (276/9956). In addition, 77.1% of cases with STRC homozygous deletions carried a two copy loss of the entire CKMT1B-STRC-CATSPER2 gene region. This information will be useful for the provision of more appropriate genetic counselling regarding hearing loss and male infertility for the patients with a STRC deletion.

scholarly journals Prevalence and Clinical Features of Autosomal Dominant and Recessive TMC1-Associated Hearing Loss.

2021 ◽  
Author(s):  
Shin-ya Nishio ◽  
Shin-ichi Usami
Keyword(s):  
Hearing Loss ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
Haplotype Analysis ◽  
Autosomal Dominant ◽  
Founder Mutation ◽  
Family Members ◽  
Causative Gene ◽  
Pathogenic Variants ◽  
Syndromic Hearing Loss

Abstract TMC1 is a causative gene for both autosomal dominant non-syndromic hearing loss (DFNA36) and autosomal recessive non-syndromic hearing loss (DFNB7/11). To date, 125 pathogenic variants in TMC1 have been reported. Most of the TMC1 variants are responsible for autosomal recessive hearing loss, with only 7 variants reported as causative for DFNA36. Here we reported the prevalence of TMC1-associated hearing loss in a large non-syndromic hearing loss cohort of about 12,000 subjects. As a result, we identified 26 probands with TMC1-associated hearing loss and the estimated prevalence of TMC1-associated hearing loss in the Japanese hearing loss cohort to be 0.18% among all patients. Among the 26 probands with TMC1-associated hearing loss, 15 cases were identified from autosomal dominant hearing loss families. By using the audiometric data from the probands, family members and previously reported cases, we evaluated the hearing deterioration speed for DFNA36 patients. In addition, we performed haplotype analysis for 11 unrelated autosomal dominant hearing loss families carrying the same variant TMC1: NM_138691:c.1627G > A:p.D543N. The results clearly indicated that the same haplotype was present despite of families being unrelated, supporting the contention that this variant occurred by founder mutation.

scholarly journals Prevalence and Characteristics of STRC Gene Mutations (DFNB16): A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Han ◽  
Dejun Zhang ◽  
Yingyuan Guo ◽  
Zeming Fu ◽  
Guofang Guan
Keyword(s):  
Systematic Review ◽  
Hearing Loss ◽  
Autosomal Recessive ◽  
Web Of Science ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Pooled Prevalence ◽  
Syndromic Hearing Loss ◽  
Moderate Hearing Loss

Background: Mutations in the STRC (MIM 606440) gene, inducing DFNB16, are considered a major cause of mild–moderate autosomal recessive non-syndromic hearing loss (ARNSHL). We conducted a systematic review and meta-analysis to determine the global prevalence and characteristics of STRC variations, important information required for genetic counseling.Methods: PubMed, Google Scholar, Medline, Embase, and Web of Science were searched for relevant articles published before January 2021.Results: The pooled prevalence of DFNB16 in GJB2-negative patients with hearing loss was 4.08% (95% CI: 0.0289–0.0573), and the proportion of STRC variants in the mild–moderate hearing loss group was 14.36%. Monoallelic mutations of STRC were 4.84% (95% CI: 0.0343–0.0680) in patients with deafness (non-GJB2) and 1.36% (95% CI: 0.0025–0.0696) in people with normal hearing. The DFNB16 prevalence in genetically confirmed patients (non-GJB2) was 11.10% (95% CI: 0.0716–0.1682). Overall pooled prevalence of deafness–infertility syndrome (DIS) was 36.75% (95% CI: 0.2122–0.5563) in DFNB16. The prevalence of biallelic deletions in STRC gene mutations was 70.85% (95% CI: 0.5824–0.8213).Conclusion: Variants in the STRC gene significantly contribute to mild–moderate hearing impairment. Moreover, biallelic deletions are a main feature of STRC mutations. Copy number variations associated with infertility should be seriously considered when investigating DFNB16.

scholarly journals Prevalence and clinical features of autosomal dominant and recessive TMC1-associated hearing loss

2021 ◽  
Author(s):  
Shin-ya Nishio ◽  
Shin-ichi Usami
Keyword(s):  
Hearing Loss ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
Haplotype Analysis ◽  
Autosomal Dominant ◽  
Founder Mutation ◽  
Family Members ◽  
Causative Gene ◽  
Pathogenic Variants ◽  
Syndromic Hearing Loss

AbstractTMC1 is a causative gene for both autosomal dominant non-syndromic hearing loss (DFNA36) and autosomal recessive non-syndromic hearing loss (DFNB7/11). To date, 125 pathogenic variants in TMC1 have been reported. Most of the TMC1 variants are responsible for autosomal recessive hearing loss, with only 8 variants reported as causative for DFNA36. Here, we reported the prevalence of TMC1-associated hearing loss in a large non-syndromic hearing loss cohort of about 12,000 subjects. As a result, we identified 26 probands with TMC1-associated hearing loss, with the estimated prevalence of TMC1-associated hearing loss in the Japanese hearing loss cohort being 0.17% among all patients. Among the 26 probands with TMC1-associated hearing loss, 15 cases were identified from autosomal dominant hearing loss families. Based on the audiometric data from the probands, family members and previously reported cases, we evaluated hearing deterioration for DFNA36 patients. In addition, we performed haplotype analysis for 11 unrelated autosomal dominant hearing loss families carrying the same variant TMC1: NM_138691:c.1627G > A:p.Asp543Asn. The results clearly indicated that the same haplotype was present despite the families being unrelated, supporting the contention that this variant occurred by founder mutation.

Sudden Sensorineural Hearing Loss in Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Clinical Review

2020 ◽  
Vol 16 (2) ◽  
pp. 84-91
Author(s):  
Julia L. Riera ◽  
María del R. Maliandi ◽  
Jorge L. Musuruana ◽  
Javier A. Cavallasca
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Clinical Feature ◽  
Systemic Lupus ◽  
Bilateral Involvement

Background: Sudden sensorineural hearing loss (SSNHL) is defined as a sudden loss of hearing, usually unilateral, of more than 30 dB in 3 contiguous frequencies of the tonal audiometry. SSNHL estimates an incidence ranging from 5 to 20 per 100.000 people per year. In approximately 75% of cases, a cause cannot be identified. However, it could be a clinical manifestation of Systemic lupus erythematosus (SLE) and Antiphospholipid Syndrome (APS). Objective: This review will focus on the clinical presentation, diagnosis, and management of the SLE and APS associated SSNHL. Methods: We searched in PubMed, Scopus, Lilacs, and Cochrane reviewing reports of Sudden sensorineural hearing loss in SLE and/or APS. Articles written in English and Spanish, and were available in full text, were included. Results: In patients with SLE, bilateral involvement was frequent. Antiphospholipid antibodies were positive in the majority of the patients. Corticosteroids were the mainstay of the treatment. The auditory prognosis was poor with total hearing loss recovery reached in only 22% of patients. : On the other hand, most of the patients with SSNHL and APS were males and presented associated symptoms such as vertigo, tinnitus and/or headache, 75% had bilateral disease. Lupus anticoagulant and aCL were found in equal proportions, all patients were anticoagulated, and aspirin was associated in 25% of the cases. Complete resolution or improvement of symptoms was observed in 25% of the patients. Conclusion: Sudden sensorineural hearing loss, can be a clinical feature of SLE and APS. Treating physicians should be aware of this devastating complication, especially when bilateral involvement occurs.

scholarly journals Sudden sensorineural hearing loss in patients with vestibular schwannoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koichiro Wasano ◽  
Naoki Oishi ◽  
Masaru Noguchi ◽  
Ko Hentona ◽  
Seiichi Shinden ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Clinical Features ◽  
Vestibular Schwannoma ◽  
Recovery Rate ◽  
Treatment Plan ◽  
Full Range ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Recurrence Time

AbstractClinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.

scholarly journals Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

2021 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Nayoung Han ◽  
Jung Mi Oh ◽  
In-Wha Kim
Keyword(s):  
Copy Number ◽  
Genome Wide Association Study ◽  
Copy Number Gain ◽  
Copy Number Variations ◽  
Gene Gain ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Haplotype Blocks ◽  
Genome Wide ◽  
Control And Prevention

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study.

scholarly journals Native α-Synuclein, 3-Nitrotyrosine Proteins, and Patterns of Nitro-α-Synuclein-Immunoreactive Inclusions in Saliva and Submandibulary Gland in Parkinson’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 715
Author(s):  
Emilio Fernández-Espejo ◽  
Fernando Rodríguez de Fonseca ◽  
Juan Suárez ◽  
Eduardo Tolosa ◽  
Dolores Vilas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Clinical Features ◽  
Clinical Feature ◽  
Similar Concentration ◽  
Duct Cells ◽  
Nitrative Stress ◽  
Salivary Concentration

Background. Salivary α-synuclein (aSyn) and its nitrated form, or 3-nitrotyrosine-α-synuclein (3-NT-αSyn), hold promise as biomarkers for idiopathic Parkinson’s disease (IPD). Nitrative stress that is characterized by an excess of 3-nitrotyrosine proteins (3-NT-proteins) has been proposed as a pathogenic mechanism in IPD. The objective is to study the pathological role of native αSyn, 3-NT-αSyn, and 3-NT-proteins in the saliva and submandibulary glands of patients with IPD. Methods. The salivary and serum αSyn and 3-NT-proteins concentration is evaluated with ELISA in patients and controls. Correlations of αSyn and 3-NT-proteins content with clinical features of the disease are examined. Immunohistochemical 3-NT-αSyn expression in submandibulary gland sections is analyzed. Results. (a) Salivary concentration and saliva/serum ratios of native αSyn and 3-NT-proteins are similar in patients and controls; (b) salivary αSyn and 3-NT-proteins do not correlate with any clinical feature; and (c) three patterns of 3-NT-αSyn-positive inclusions are observed on histological sections: rounded “Lewy-type” aggregates of 10–25 µm in diameter, coarse deposits with varied morphology, and spheroid inclusions or bodies of 3–5 µm in diameter. “Lewy-type” and coarse inclusions are observed in the interlobular connective tissue of the gland, and small-sized bodies are located within the cytoplasm of duct cells. “Lewy-type” inclusions are only observed in patients, and the remaining patterns of inclusions are observed in both the patients and controls. Conclusions. The patients’ saliva presents a similar concentration of native αSyn and 3-nitrotyrosine-proteins than that of the controls, and no correlations with clinical features are found. These findings preclude the utility of native αSyn in the saliva as a biomarker, and they indicate the absence of nitrative stress in the saliva and serum of patients. As regards nitrated αSyn, “Lewy-type” inclusions expressing 3-NT-αSyn are observed in the patients, not the controls—a novel finding that suggests that a biopsy of the submandibulary gland, if proven safe, could be a useful technique for diagnosing IPD. Finally, to our knowledge, this is also the first description of 3-NT-αSyn-immunoreactive intracytoplasmic bodies in cells that are located outside the nervous system. These intracytoplasmic bodies are present in duct cells of submandibulary gland sections from all subjects regardless of their pathology, and they can represent an aging or involutional change. Further immunostaining studies with different antibodies and larger samples are needed to validate the data.

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