scholarly journals Genetic linkage analysis of DFNB22 in families with autosomal recessive non-syndromic hearing loss in Khuzestan province

2019 ◽  
Vol 21 (5) ◽  
pp. 200-203
Author(s):  
Ladan Sadeghian ◽  
Mohammad Amin Tabatabaiefar ◽  
Morteza Hashemzadeh Chaleshtori
Keyword(s):  
Hearing Loss ◽  
Linkage Analysis ◽  
Autosomal Recessive ◽  
Polyacrylamide Gel Electrophoresis ◽  
Genetic Linkage Analysis ◽  
Haplotype Reconstruction ◽  
Limited Information ◽  
Khuzestan Province ◽  
Syndromic Hearing Loss

Background and aims: Hearing loss (HL) is the most common sensorineural disorder affecting 1 in 1000 newborns. Autosomal recessive non-syndromic hearing loss (ARNSHL), which is the most common cause of severe HL, is caused by mutations in more than 80 loci. The OTOA gene located on DFNB22 is a rare cause of the disease and the gene studied less in Iranian ARNSHL families. Hence, limited information is available on the frequency and type of OTOA mutations in different populations. In this study, we investigated the role of DFNB22 locus in ARNSHL patients in Khuzestan province, Iran. Materials and Methods: In this descriptive-experimental study, 23 large families with pre-lingual ARNSHL from Khuzestan province were enrolled. Mutations in GJB2 were excluded by DNA sequencing followed by linkage analysis. Homozygosity mapping of DFNB22 was conducted using 6 short tandem repeat polymorphic markers via touch-down PCR and polyacrylamide gel electrophoresis. Homozygosityby-descent was identified by calculating two-point and multi-point LOD score and haplotype reconstruction. Results: Families were negative for GJB2 mutations. Genotyping the STRP markers, haplotype reconstruction, and two-point and multiplepoint LOD scores did not show homozygosity-by-descent in any of the pedigrees. Conclusion: Our findings suggest that OTOA mutations might not contribute significantly to the molecular pathophysiology of ARNSHL in Khuzestan province. However, extending the sample size can illuminate the role of this gene in Khuzestan province.

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations

2020 ◽  
Author(s):  
Mahbobeh KOOHIYAN ◽  
Somayeh REIISI ◽  
Fatemeh AZADEGAN-DEHKORDI ◽  
Mansoor SALEHI ◽  
Hamidreza ABTAHI ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Homozygosity Mapping ◽  
Gjb2 Gene ◽  
Global Public Health ◽  
Relative Contribution ◽  
Syndromic Hearing Loss ◽  
High Degree ◽  
Gjb2 Mutations

Background: Autosomal recessive non-syndromic hearing loss (ARNSHL), one of the global public health concerns, is marked by a high degree of genetic heterogeneity. The role of GJB2, as the most common cause of ARNSHL, is only <20% in the Iranian population. Here, we aimed to determine the relative contribution of several apparently most common loci in a cohort of ARNSHL Iranian families that were negative for the GJB2 mutations. Methods: Totally, 80 Iranian ARNSHL families with 3 or more affected individuals from Isfahan and Hamedan provinces, Iran were enrolled in 2017. After excluding mutations in the GJB2 gene via Sanger sequencing, 60 negative samples (30 families from each province) were analyzed using homozygosity mapping for 10 ARNSHL loci. Results: Fourteen families were found to be linked to five different known loci, including DFNB4 (5 families), DFNB2 (3 families), DFNB7/11 (1 family), DFNB9 (2 families) and DFNB3 (3 families). Conclusion: Despite the high heterogeneity of ARNSHL, the genetic causes were determined in 23.5% of the studied families using homozygosity mapping. This data gives an overview of the ARNSHL etiology in the center and west of Iran, used to establish a diagnostic gene panel including most common loci for hearing loss diagnostics.

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 Frequency of GJB2 mutations in families with autosomal recessive non-syndromic hearing loss in Khuzestan province

Genetika ◽  
2018 ◽  
Vol 50 (3) ◽  
pp. 837-846
Author(s):  
Parisa Tahmasebi ◽  
Morteza Chaleshtori Hashemzadeh ◽  
Fatemeh Abdollahnejad ◽  
Zahra Alavi ◽  
Ladan Sadeghian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Khuzestan Province ◽  
Syndromic Hearing Loss ◽  
Gjb2 Mutations

scholarly journals Lights and Shadows in the Genetics of Syndromic and Non-Syndromic Hearing Loss in the Italian Population

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1237
Author(s):  
Anna Morgan ◽  
Stefania Lenarduzzi ◽  
Beatrice Spedicati ◽  
Elisabetta Cattaruzzi ◽  
Flora Maria Murru ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Disease Genes ◽  
Italian Population ◽  
Essential Information ◽  
Whole Exome ◽  
Relevant Role ◽  
Multiplex Ligation Probe Amplification ◽  
Syndromic Hearing Loss

Hearing loss (HL), both syndromic (SHL) and non-syndromic (NSHL), is the most common sensory disorder, affecting ~460 million people worldwide. More than 50% of the congenital/childhood cases are attributable to genetic causes, highlighting the importance of genetic testing in this class of disorders. Here we applied a multi-step strategy for the molecular diagnosis of HL in 125 patients, which included: (1) an accurate clinical evaluation, (2) the analysis of GJB2, GJB6, and MT-RNR1 genes, (3) the evaluation STRC-CATSPER2 and OTOA deletions via Multiplex Ligation Probe Amplification (MLPA), (4) Whole Exome Sequencing (WES) in patients negative to steps 2 and 3. Our approach led to the characterization of 50% of the NSHL cases, confirming both the relevant role of the GJB2 (20% of cases) and STRC deletions (6% of cases), and the high genetic heterogeneity of NSHL. Moreover, due to the genetic findings, 4% of apparent NSHL patients have been re-diagnosed as SHL. Finally, WES characterized 86% of SHL patients, supporting the role of already know disease-genes. Overall, our approach proved to be efficient in identifying the molecular cause of HL, providing essential information for the patients’ future management.

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

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

An update of common autosomal recessive non-syndromic hearing loss genes in Iranian population

2017 ◽  
Vol 97 ◽  
pp. 113-126 ◽  
Author(s):  
Tohid Ghasemnejad ◽  
Mahmoud Shekari Khaniani ◽  
Fatemeh Zarei ◽  
Mina Farbodnia ◽  
Sima Mansoori Derakhshan
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Iranian Population ◽  
Syndromic Hearing Loss

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

scholarly journals Targeted Next-Generation Sequencing of a Deafness Gene Panel (MiamiOtoGenes) Analysis in Families Unsuitable for Linkage Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Haiqiong Shang ◽  
Denise Yan ◽  
Naeimeh Tayebi ◽  
Kolsoum Saeidi ◽  
Afsaneh Sahebalzamani ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Linkage Analysis ◽  
Autosomal Recessive ◽  
Target Sequence ◽  
Novel Mutations ◽  
Nonsyndromic Deafness ◽  
Targeted Next Generation Sequencing ◽  
Deafness Gene ◽  
Comprehensive Diagnosis ◽  
Generation Sequencing

Hearing loss (HL) is a common sensory disorder in humans with high genetic heterogeneity. To date, over 145 loci have been identified to cause nonsyndromic deafness. Furthermore, there are countless families unsuitable for the conventional linkage analysis. In the present study, we used a custom capture panel (MiamiOtoGenes) to target sequence 180 deafness-associated genes in 5 GJB2 negative deaf probands with autosomal recessive nonsyndromic HL from Iran. In these 5 families, we detected one reported and six novel mutations in 5 different deafness autosomal recessive (DFNB) genes (TRIOBP, LHFPL5, CDH23, PCDH15, and MYO7A). The custom capture panel in our study provided an efficient and comprehensive diagnosis for known deafness genes in small families.

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