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 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.

Nonsyndromic Hearing Loss: An Analysis of Audiograms

1994 ◽  
Vol 103 (6) ◽  
pp. 428-433 ◽  
Author(s):  
Xuezhong Liu ◽  
Lirong Xu
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Family Members ◽  
Nonsyndromic Hearing Loss ◽  
Significant Difference ◽  
Genetic Hearing Loss ◽  
Group Information

We examined features of the audiograms of 136 individuals, from 28 families, affected by nonsyndromic genetic hearing loss. There were 83 (12 families) with autosomal dominant (AD) loss, 50 (15 families) with autosomal recessive (AR) loss, and 3 (1 family) with X-linked recessive loss. The main audiogram shapes found were sloping (50.3%), residual (26.5%), and flat (21.0%). Specific shapes (ascending and U-shaped) only occurred in 3.7% of AD cases. Audiogram shapes were found to be significantly different between AD and AR families, and showed intrafamilial and interfamilial variability. In the AR group, the main shapes were residual and sharply sloping, and in the AD group, sharply sloping, flat, and gently sloping. There was a significant difference in the degree of hearing loss between AD and AR types, with AD being milder than AR. It has been shown that there is more marked intrafamilial variation in the degree of hearing loss in AD families than in AR ones. The results suggest that the audiograms of nonsyndromic hearing loss are usually nonspecific and that counseling of family members would be better based on the specific family's condition rather than on group information.

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 Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1467
Author(s):  
Gema García-García ◽  
Alba Berzal-Serrano ◽  
Piedad García-Díaz ◽  
Rebeca Villanova-Aparisi ◽  
Sara Juárez-Rodríguez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Targeted Ngs ◽  
Syndromic Hearing Loss ◽  
Genetics And Genomics ◽  
Custom Panel ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare.

Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in TMC1 Gene

2020 ◽  
pp. 1-7
Author(s):  
Samanta Gallo ◽  
Patrizia Trevisi ◽  
Chiara Rigon ◽  
Ezio Caserta ◽  
Dario Seif Ali ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Functional Outcome ◽  
Cochlear Implantation ◽  
Autosomal Recessive ◽  
Pediatric Patients ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Excellent Functional Outcome ◽  
Speech Performance ◽  
Syndromic Hearing Loss

<b><i>Introduction:</i></b> Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in <i>TMC1</i> gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. <b><i>Methods:</i></b> A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in <i>TMC1</i> were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. <b><i>Results:</i></b> DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in <i>TMC1</i> was detected [c.962G&#x3e;A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. <b><i>Discussion/Conclusion:</i></b> Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.

scholarly journals First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Dominika Oziębło ◽  
Anna Sarosiak ◽  
Marcin L. Leja ◽  
Birgit S. Budde ◽  
Grażyna Tacikowska ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Linkage Analysis ◽  
Segregation Analysis ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
German Family ◽  
Clinical Exome Sequencing ◽  
Genome Wide ◽  
Syndromic Hearing Loss ◽  
Family Segregation

Abstract Background Biallelic PTPRQ pathogenic variants have been previously reported as causative for autosomal recessive non-syndromic hearing loss. In 2018 the first heterozygous PTPRQ variant has been implicated in the development of autosomal dominant non-syndromic hearing loss (ADNSHL) in a German family. The study presented the only, so far known, PTPRQ pathogenic variant (c.6881G>A) in ADNSHL. It is located in the last PTPRQ coding exon and introduces a premature stop codon (p.Trp2294*). Methods A five-generation Polish family with ADNSHL was recruited for the study (n = 14). Thorough audiological, neurotological and imaging studies were carried out to precisely define the phenotype. Genomic DNA was isolated from peripheral blood samples or buccal swabs of available family members. Clinical exome sequencing was conducted for the proband. Family segregation analysis of the identified variants was performed using Sanger sequencing. Single nucleotide polymorphism array on DNA samples from the Polish and the original German family was used for genome-wide linkage analysis. Results Combining clinical exome sequencing and family segregation analysis, we have identified the same (NM_001145026.2:c.6881G>A, NP_001138498.1:p.Trp2294*) PTPRQ alteration in the Polish ADNSHL family. Using genome-wide linkage analysis, we found that the studied family and the original German family derive from a common ancestor. Deep phenotyping of the affected individuals showed that in contrast to the recessive form, the PTPRQ-related ADNSHL is not associated with vestibular dysfunction. In both families ADNSHL was progressive, affected mainly high frequencies and had a variable age of onset. Conclusion Our data provide the first confirmation of PTPRQ involvement in ADNSHL. The finding strongly reinforces the inclusion of PTPRQ to the small set of genes leading to both autosomal recessive and dominant hearing loss.

scholarly journals High prevalence of theW24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss

2005 ◽  
Vol 137A (3) ◽  
pp. 255-258 ◽  
Author(s):  
Araceli Álvarez ◽  
Ignacio del Castillo ◽  
Manuela Villamar ◽  
Luis A. Aguirre ◽  
Anna González-Neira ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Connexin 26 ◽  
Gene Encoding ◽  
High Prevalence ◽  
Syndromic Hearing Loss

scholarly journals Genetic hearing loss: a study of 228 Brazilian patients

2000 ◽  
Vol 23 (1) ◽  
pp. 25-27 ◽  
Author(s):  
Silvia Bragagnolo Longhitano ◽  
Décio Brunoni
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Inheritance ◽  
Recessive Inheritance ◽  
Dominant Inheritance ◽  
Genetic Etiology ◽  
Parental Consanguinity ◽  
Genetic Hearing Loss ◽  
Associated Abnormalities

We studied 228 patients, with suspected or confirmed genetic hearing loss, in order to determine the clinical and genetic diagnoses and etiology of each case. Deafness with no associated abnormalities was found in 146 patients (64%) belonging to 112 families. Syndromic deafness was diagnosed in 82 patients (36%) belonging to 76 families. The genetic etiology was as follows: autosomal recessive inheritance in 40.8% of syndromics and non-syndromics, autosomal dominant inheritance in 13.2% and X-linked recessive in 1.3%. In 44.7% of the cases, the etiology of the hearing loss could not be determined. Monogenic causes are the most possible etiology in the latter cases. Parental consanguinity was found in 22.4% of the cases, and deafness was bilateral, profound and neurosensorial in 47.4% of the patients. An early onset of hearing loss (< 2 years of age) occurred in 46.5% of the cases. These results are similar to previous literature reports.

Decreased disulphide/thiol ratio in patients with autosomal recessive non-syndromic hearing loss

2018 ◽  
Vol 112 ◽  
pp. 188-192
Author(s):  
Burhan Balta ◽  
Ramazan Gundogdu ◽  
Murat Erdogan ◽  
Murat Alisik ◽  
Aslihan Kiraz ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Syndromic Hearing Loss
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