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.

GJB2 mutations causing autosomal recessive non-syndromic hearing loss (ARNSHL) in two Iranian populations: Report of two novel variants

2018 ◽  
Vol 107 ◽  
pp. 121-126 ◽  
Author(s):  
Mahbobeh Koohiyan ◽  
Morteza Hashemzadeh-Chaleshtori ◽  
Mansoor Salehi ◽  
Hamidreza Abtahi ◽  
Somayeh Reiisi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Novel Variants ◽  
Syndromic Hearing Loss ◽  
Gjb2 Mutations ◽  
Iranian Populations

High frequency of heterozygosity in GJB2 mutations among patients with non-syndromic hearing loss

2008 ◽  
Vol 123 (3) ◽  
pp. 273-277 ◽  
Author(s):  
G Khandelwal ◽  
S Bhalla ◽  
M Khullar ◽  
N K Panda
Keyword(s):  
Hearing Loss ◽  
Indian Population ◽  
Gjb2 Gene ◽  
Coding Region ◽  
Syndromic Hearing Loss ◽  
Polymerase Chain ◽  
35Delg Mutation ◽  
Control Study ◽  
Gjb2 Mutations ◽  
Prevalent Mutation

AbstractObjective:To determine the prevalence of GJB2 mutations among subjects with congenital, non-syndromic, sensorineural hearing loss, within a north Indian population.Materials and methods:This was a case–control study in which the frequencies of the three most prevalent GJB2 mutations (35delG, W24X and 167delT) were studied. Polymerase chain reaction restriction fragment length polymorphism assays were performed to detect these mutations. The entire coding region of the GJB2 gene was sequenced in all patients, and also in any of their family members who showed GJB2 mutations.Results:The 35delG mutation was found to be the most prevalent mutation (21 per cent), followed by the W24X mutation (7 per cent). This is the first report of the 35delG mutation in an Indian population. One patient was a compound heterozygote for 35delG/W24X. The 167delT mutation was not observed in any patient.Conclusions:These findings challenge the classical view that the W24X variant of the GJB2 gene represents a single ‘founder’ mutation.

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.

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

scholarly journals Whole-Genome Sequencing Improves the Diagnosis of DFNB1 Monoallelic Patients

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1267
Author(s):  
Anaïs Le Nabec ◽  
Mégane Collobert ◽  
Cédric Le Maréchal ◽  
Rémi Marianowski ◽  
Claude Férec ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Gjb2 Gene ◽  
Whole Genome ◽  
Genetic Origin ◽  
Functional Assays ◽  
Syndromic Hearing Loss ◽  
Sensory Defect

Hearing loss is the most common sensory defect, due in most cases to a genetic origin. Variants in the GJB2 gene are responsible for up to 30% of non-syndromic hearing loss. Today, several deafness genotypes remain incomplete, confronting us with a diagnostic deadlock. In this study, whole-genome sequencing (WGS) was performed on 10 DFNB1 patients with incomplete genotypes. New variations on GJB2 were identified for four patients. Functional assays were realized to explore the function of one of them in the GJB2 promoter and confirm its impact on GJB2 expression. Thus, in this study WGS resolved patient genotypes, thus unlocking diagnosis. WGS afforded progress and bridged some gaps in our research.

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