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

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.

Download Full-text

Investigating GJB2 Mutation in 31 Individuals With Non-syndromic Hearing Loss

Journal of Arak University of Medical Sciences ◽

10.32598/jams.24.1.4277.6 ◽

2021 ◽

Vol 24 (1) ◽

pp. 50-61

Author(s):

Pedram Pouryari Biyachal ◽

◽

Najmeh Ranji ◽

Ali Nazemi ◽

◽

...

Keyword(s):

Hearing Loss ◽

Cross Sectional Study ◽

Gjb2 Gene ◽

Common Mutation ◽

Cross Sectional ◽

Gjb2 Mutation ◽

Syndromic Hearing Loss ◽

Pcr Method ◽

Gilan Province ◽

35Delg Mutation

Background and Aim: Non-syndromic hearing loss is a genetically heterogeneous disorder. Mutation in the GJB2 gene is a major cause of non-syndromic hearing loss in numerous countries. This study aimed to evaluate GJB2 mutations in 31 individuals with non-syndromic hearing loss Methods & Materials: In this descriptive cross-sectional study, the required blood samples were collected from 31 individuals with non-syndromic hearing loss in Rasht and Bandar Anzali Cities, Gilan Province, Iran. After DNA isolation, the GJB2 gene was amplified by the PCR method and underwent sequencing. Ethical Considerations:This study was approved by the Ethics Committee of the Islamic Azad University, Mashhad Branch (Code: IR.IAU.MSHD.REC.1398.027). Results: In this study, 3 mutations were determined in 18 individuals with hearing loss. Accordingly, 35delG mutation had the highest frequency (48.38%) in individuals with hearing loss as homozygote (n=14) and heterozygote (n=2). A patient with heterozygosity in V153I mutation and a patient with compound heterozygosity in 35delG/G200R mutation was determined. Conclusion: It appears that 35delG mutation is a common mutation in the GJB2 gene in individuals with non-syndromic hearing loss in Guilan Province.

Download Full-text

GJB2 Mutations in Non Syndromic Hearing Loss in the Republic of Macedonia

Balkan Journal of Medical Genetics ◽

10.2478/v10034-010-0004-x ◽

2009 ◽

Vol 12 (2) ◽

pp. 11-16

Author(s):

E Stefanovska ◽

A Momirovska ◽

M Cakar ◽

G Efremov

Keyword(s):

Hearing Loss ◽

Direct Sequencing ◽

Single Strand Conformation Polymorphism ◽

Republic Of Macedonia ◽

Profound Deafness ◽

Syndromic Hearing Loss ◽

Prelingual Deafness ◽

The Republic ◽

35Delg Mutation ◽

Gjb2 Mutations

GJB2 Mutations in Non Syndromic Hearing Loss in the Republic of MacedoniaHearing impairment is a common sensori-neural disorder with the incidence of profound deafness in one per 1,000 births. Non syndromic recessive deafness (NSHL), accounts for approximately 80% of cases of hereditary deafness. It is extremely heterogeneous genetically with over 130 gene loci. Mutations in the GJB2 and GJB6 genes for DFNB1 locus (13q12) are responsible for about half of all cases of autosomal recessive prelingual hearing loss.We determined the prevalence and mutations in the GJB2 gene, and the presence of delD13S1830 in the GJB6 gene in DNA samples from 33 unrelated Macedonian families with recesive NSHL and 200 normal hearing individuals using single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing and specific polymerase chain reaction (PCR).We found mutations in the GJB2 gene in 12 patients, but no delD13S1830 in the GJB6 gene. In 22 mutated chromosomes, 15 (68.2%) had the 35delG mutation, four (6.1%) W24X, two (3.0%) V37I and one (1.5%) R127H.Because of the high mutation rate (36.4%) in the GJB2 gene in NSHL patients, testing should be performed in all cases with prelingual deafness.

Download Full-text

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

Iranian Journal of Public Health ◽

10.18502/ijph.v48i9.3031 ◽

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.

Download Full-text

Mutation in second exon of MYO15A gene cause of nonsyndromic hearing loss and its association in the Arab population in Iran

Genetika ◽

10.2298/gensr1602587a ◽

2016 ◽

Vol 48 (2) ◽

pp. 587-596 ◽

Cited By ~ 4

Author(s):

Samira Asgharzade ◽

Morteza Chaleshtori ◽

Mohammad Tabatabaifar ◽

Somayeh Reisi ◽

Mohammad Modaressi

Keyword(s):

Hearing Loss ◽

Gene Mutations ◽

Amino Acid Position ◽

Gjb2 Gene ◽

Coding Region ◽

Arab Population ◽

Exon 2 ◽

Direct Dna Sequencing ◽

Syndromic Hearing Loss ◽

Southwest Of Iran

Hearing loss is a genetically and clinically heterogeneous defect and more than 140 loci and 65 genes have been identified to cause autosomal recessive non-syndromic hearing loss (ARNSHL). According to the previous studies, mutations in GJB2 are estimated to be involved in 18.17% of ARNSHL cases in the Iranian population; as a result, the remaining 81.83% of this disorder is yet ambiguous. This study aimed to determine the contribution of DFNB3 in hearing loss as well as the frequency of gene mutations in a population (Arab tribal origin) in the Southwest of Iran. In this descriptive laboratory study, we included 25 families from the Southwest of Iran and negative GJB2 gene. Linkage analysis was performed by DFNB3 (MYO15A) molecular markers (STR). The families with hearing loss linked to this locus were further analyzed for mutation detection. MYO15A gene exons were amplified and analyzed using direct DNA sequencing. In studied families, one family displayed linkage to DFNB3 locus. Identified mutations include substitution and substitute C for A in 1047 location of coding region of MYO15A gene (c.1047 C>A) in exon 2 which cause to change Tyrosin to stop codons (P.Y349X), results in the premature truncation at amino acid position 349.

Download Full-text

Role of Genetic Factors in the Causation of Non-Syndromic Hearing Loss (NSHL) in Indian Population

Archives of Clinical and Biomedical Research ◽

10.26502/acbr.50170143 ◽

2020 ◽

Vol 04 (06) ◽

Author(s):

Shehnaz Sultana ◽

Pratibha Nallari ◽

Venkateshwari Ananthapur

Keyword(s):

Hearing Loss ◽

Indian Population ◽

Genetic Factors ◽

Syndromic Hearing Loss

Download Full-text

Prevalence of congenital non syndromic hearing loss among offspring of consanguineous marriage: a pilot study

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20201677 ◽

2020 ◽

Vol 6 (5) ◽

pp. 874

Author(s):

Gangadhar K. S. ◽

Geetha Bhaktha ◽

Manjula B. ◽

Nageshwari P.

Keyword(s):

Hearing Loss ◽

Consanguineous Marriage ◽

Gene Encoding ◽

Single Nucleotide ◽

Junction Protein ◽

Study Population ◽

Syndromic Hearing Loss ◽

Gap Junction Protein ◽

Polymerase Chain ◽

Recessive Defect

Background: Mutations in the gene encoding the gap-junction protein connexin-26, is understood to be the most important cause of non-syndromic hearing loss (NSHL). An attempt to identify the single nucleotide polymorphism (SNP) for W24X mutation was done. Consanguineous marriage was seen among the NSHL subjects.Methods: SNP was identified using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Forty-five subjects were screened for congenital hearing loss. Twenty subjects matched the inclusion criteria and were included in the study.Results: 5 out of 20 subjects were found to have mutation i.e., 25%. Though consanguinity is known to cause autosomal recessive defect, the same could not be depicted in this study.Conclusions: 25% of the study population had a mutation in their gene and the rest though had consanguineous marriage had not been affected genotypically.

Download Full-text

Whole-Genome Sequencing Improves the Diagnosis of DFNB1 Monoallelic Patients

Genes ◽

10.3390/genes12081267 ◽

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.

Download Full-text

Association of IL13R Alpha 1 + 1398A/G Polymorphism in a North Indian Population with Asthma: A Case-Control Study

Allergy & Rhinology ◽

10.2500/ar.2015.6.0126 ◽

2015 ◽

Vol 6 (2) ◽

pp. ar.2015.6.0126

Author(s):

Shweta Sinha ◽

Jagtar Singh ◽

Surinder Kumar Jindal ◽

Niti Birbian

Keyword(s):

Indian Population ◽

Immunoglobulin E ◽

Airway Hyperreactivity ◽

Total Serum ◽

North Indian Population ◽

Increased Risk ◽

Asthma Patients ◽

Polymerase Chain ◽

Control Study

Background Interleukin 13 (IL13) is directly involved in the secretion of total serum immunoglobulin E (IgE), which plays a major role in the asthma pathogenesis. Objective One of the polymorphic receptor of IL13 is IL13Rα1, which after binding to IL13, initiates signal transduction that results in mucin secretion, airway hyperreactivity, fibrosis, and chitinase up-regulation, which increases asthma risk. Methods In the present study, the role of IL13Rα1 + 1398A/G gene polymorphisms in asthma was detected with a total of 964 individuals, including 483 healthy controls and 481 asthma patients from a North Indian population using polymerase chain reaction-restriction fragment length polymorphism method. Results Statistical analysis revealed that the mutant allele (G) is predominant in asthma patients (42.7%) than the controls (38.2%), which shows an increased risk toward asthma with odds ratio = 1.21, 95% confidence interval (1.00 −1.45), χ2 = 4.10 and p = 0.043. Furthermore, the phenotypic characteristics also reveal a significant association with the disease (p < 0.05). Conclusions This is the first study conducted in India and + 1398A/G polymorphism in noncoding region of IL13Rα1 confer risk toward asthma in the studied population.

Download Full-text