A novel frameshift mutation (c.405delC) in the GJB2 gene associated with autosomal recessive hearing loss in two Tunisian families

2013 ◽  
Vol 77 (9) ◽  
pp. 1485-1488 ◽  
Author(s):  
Zied Riahi ◽  
Houda Chahed ◽  
Habib Jaafoura ◽  
Rim Zainine ◽  
Olfa Messaoud ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Frameshift Mutation ◽  
Gjb2 Gene

Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss

Gene ◽  
2013 ◽  
Vol 525 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Zied Riahi ◽  
Hassen Hammami ◽  
Houyem Ouragini ◽  
Habib Messai ◽  
Rim Zainine ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Gjb2 Gene ◽  
Nonsyndromic Hearing Loss

scholarly journals Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

2021 ◽  
pp. 98-98
Author(s):  
Bojana Dobric ◽  
Danijela Radivojevic ◽  
Jovana Jecmenica ◽  
Vassos Neocleous ◽  
Pavlos Fanis ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Phenotype Correlation ◽  
Pathogenic Variants ◽  
Environmental Causes ◽  
35Delg Mutation

Introduction/Objective. Hearing impairment (HI) is the most common sensorineural disorder with an incidence of 1/700-1000 newborns. Variants in the GJB2 gene are the major cause of autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). The degree of HI in patients with detected mutations in GJB2 gene ranges from mild to profound. The aim of this study was to determine possible genotype-phenotype association between audiometric characteristics and detected genotypes in ARNSHL patients from Serbia. Methods. Ninety-two patients with ARNSHL underwent genetic analysis with PCR-ARMS and sequencing of the GJB2 gene. Audiological analyses were obtained in all patients using a combination of several methods to estimate the degree of hearing loss. Results. Audiological analysis performed in the 92 probands showed moderate to profound range of hearing loss. All identified pathogenic variants accounted for 42.39% of the mutant alleles (78/184 alleles), with the c.35delG mutation being the most frequent (30.43%). Genotype-phenotype correlation in an isolated group of 37 patients bearing c.35delG in the homozygous, compound heterozygous or heterozygous state. In this group the majority of patients (30/37, 81.08%) exhibited severe to profound hearing deficit. Conclusion. Association between genotype and the degree of hearing impairment in patients analyzed in this study demonstrated that patients with bi-allelic truncating mutations i.e. c.35delG, associate with the more severe hearing loss when compared with those identified with only one affected allele. The various degrees of hearing impairment observed in heterozygous patients could be explained by the presence of an undetected second mutation or other modifier genes or environmental causes.

scholarly journals Connexin 26 (GJB2) Gene Mutations Linked With Autosomal Recessive Nonsyndromic Sensorineural Hearing Loss in Iraqi Population

2021 ◽  
Author(s):  
Anwar Madlool Al-janabi ◽  
Habeeb Shuhaib Ahmmed ◽  
Salih Mahdi Al-Khafaji
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Sensorineural Deafness ◽  
Healthy Control Group ◽  
Gjb2 Gene ◽  
Connexin 26 ◽  
Control Group ◽  
Current Case ◽  
Healthy Control

Abstract Background:Deafness is a total or partial hearing loss that may appear at any ages with different degrees of severity. Approximately 50% of hearing loss have a genetic origin, among them, the nonsyndromic sensorineural deafness represents about 70% of the cases. From them 80% corresponding to autosomal recessive inheritance deafness. Objective: Autosomal recessive deafness was not been studied enough at molecular level in Iraq, so this study aimed to detect the prevalence of the three most common mutations of Connexin 26 (GJB2) gene in nonsyndromic sensorineural deafness for Iraqi population.Method: The current case-control study was conducted from January 2018 to January 2020 at molecular laboratory in Anatomy and Histology Department/ faculty of Medicine/ Kufa University/Najaf/ Iraq. The study was included 95 deaf patients (55 males and 40 females) their age range between 11-40 years old and 21.5 ± 6.3 year (mean ± SD) and 110 healthy control group, their ages range between 10-40 years old and 20.1 ± 5.9 year (mean ± SD), these two groups were matched in age and gender. In order to detect c.35delG, 235delC and 167delT mutations in GJB2 gene, we were employed the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technique.Results: From 95 deaf patients with ARNSHL who were participated in this study, the c.35delG was the main frequent mutation encountered with GJB2 gene, among them 35(36.8%) were homozygous, 40(42.1%) were heterozygous and 20 (21.1%) were wild genotypes. The second degree mutation in GJB2 gene was c.235delC mutation, which from the 95 deaf patients, there were 21 (22.1%) carried out homozygous, 33 (34.7%) heterozygous and 42(44.2%) wild genotypes. None of the 95 deaf patients were showed the c.167delT mutation, on the other hand these variants were not detected in healthy control group which was studied parallel with patients group.Conclusion: Our data conclude that the GJB2 c.35delG and c.235delC gene mutations were the main cause of ARNSHL in Iraqi deaf population.

scholarly journals A novel nonsense mutation c.1121G>A (p.Trp374*) in the CLIC5 gene is the main cause of the juvenile autosomal recessive form of deafness (DFNB103) in the Arctic regions of Yakutia

2019 ◽  
pp. 36-48
Author(s):  
В.Г. Пшенникова ◽  
Г.П. Романов ◽  
Т.М. Николаева ◽  
Ф.М. Терютин ◽  
Т.В. Борисова ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Disease Onset ◽  
Premature Stop Codon ◽  
The Arctic ◽  
Gjb2 Gene ◽  
Unknown Etiology ◽  
Homozygous Mutation ◽  
Homozygous Variant ◽  
First Case

Наиболее частой причиной несиндромальной потери слуха являются мутации гена GJB2. Ранее было показано, что в Якутии вклад мутаций гена GJB2 в потерю слуха среди пациентов с врожденной тугоухостью составил 49%. Целью данной работы являлся поиск молекулярно-генетических основ потери слуха среди GJB2-негативных пациентов, у которых причина заболевания осталась неустановленной. В исследование были включены 238 (228 неродственных) GJB2-негативных пациентов, среди которых мы обнаружили одну семью с 5 пораженными индивидами с ювенильной потерей слуха неизвестной этиологии (дебют заболевания варьировал от 0 до 8 лет). Путём полноэкзомного анализа (WES), проведенного у одного из пораженных членов семьи, была выявлена ранее не описанная гомозиготная замена c.1121G>A в 6-ом экзоне гена CLIC5 (6p21.1, OMIM 607293). Данная транзиция приводит к образованию преждевременного стоп-кодона в 374-ой аминокислотной позиции (p.Trp374*), терминирующего синтез полипептидной цепи белка CLIC5 (NP_001107558.1). В гене CLIC5 известна только одна гомозиготная замена c.96T>A (р.Cys32*), которая ранее была найдена в инбредной турецкой семье с постлингвальной прогрессирующей аутосомно-рецессивной глухотой (DFNB103). В настоящей работе гомозиготный вариант c.1121G>A (p.Trp374*) был выявлен у 26 из 238 GJB2-негативных пациентов (10,9%). У большинства из них (19 из 26) отмечается поздний дебют потери слуха в среднем в 9,7±0,6 лет. Аудиологическое обследование у 13 из 26 пациентов выявило преимущественно симметричную сенсоневральную прогрессирующую потерю слуха различной степени тяжести (от донозологической и I-ой степени тугоухости до глухоты). Распространенность DFNB103, обусловленной гомозиготным вариантом c.1121G>A (p.Trp374*) гена CLIC5, в Якутии составила в среднем 0,27±0,05 на 10000 человек с максимальным накоплением в Эвено-Бытантайском национальном районе (31,39±10,46 на 10000 человек), который относится к арктической группе улусов, где большинство населения составляют эвены (53%). Это первый в России случай идентификации орфанного заболевания, накопление которого обнаружено в Арктике. В целом, гомозиготный вариант c.1121G>A (p.Trp374*) гена CLIC5 можно расценивать как каузативный для DFNB103 с высоким вкладом в этиологию нарушений слуха у населения Якутии. The most common cause of non-syndromic hearing loss in various populations of the world is the mutations in the GJB2 gene. Previously it was shown that the pathogenic contribution of the GJB2-mutations among patients with congenital hearing loss in Yakutia was 49%. The aim of this work was to investigate the molecular genetic basis of hearing loss among GJB2-negative patients. The study included 238 (228 unrelated) GJB2-negative patients, among them we found one family with five affected individuals with juvenile hearing loss of unknown etiology (the disease onset varied from 0 to 8 years). Using a whole exome sequencing (WES), performed in one of affected family members, a novel homozygous c.1121G>A (6p21.1, OMIM 607293) substitution in exon 6 of the CLIC5 gene was detected. This substitution leads to the formation of a premature stop codon at the 374 amino acid position (p.Trp374*) which terminates the synthesis of the polypeptide chain of the CLIC5 protein (NP_001107558.1). To date, only one homozygous mutation c.96T>A (p.Cys32*) was known in human gene CLIC5 which was found in one inbred Turkish family with progressive autosomal recessive deafness, type 103 (DFNB103). In our study, a homozygous variant c.1121G>A (p.Trp374*) was detected in 26 out of 238 GJB2-negative patients in Yakutia (10.9%). Most of homozygous for c.1121G>A patients (19 out of 26) reported about late onset of their hearing loss occurred in postlingual period (averaged 9.7±0.6 years). Audiological examination of 13 out of 26 patients revealed predominantly symmetric sensorineural progressive hearing loss of varying severity (from mild to profound hearing loss). The average prevalence of DFNB103 caused by the homozygous variant c.1121G>A (p.Trp374*) in Yakutia was 0.27±0.053 per 10000 with a maximum accumulation in Eveno-Bytantaysky district (31.39±10.46 per 10000) which referred to the Arctic group of districts where the majority of the population is represented by Evens (53%). This is the first case of the identification of the orphan disease with its accumulation in Arctic part of Russia. In general, the homozygous variant c.1121G>A (p.Trp374*) of the CLIC5 gene can be regarded as causative to DFNB103 with a high contribution to the etiology of hearing impairments in the population of Yakutia.

Hearing loss associated with 35delG mutation in Connexin-26 (GJB2) gene: audiogram analysis

2004 ◽  
Vol 118 (1) ◽  
pp. 8-11 ◽  
Author(s):  
Fabrizio Salvinelli ◽  
Manuele Casale ◽  
Luca D’Ascanio ◽  
Luca Firrisi ◽  
Fabio Greco ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Pure Tone Audiometry ◽  
Gjb2 Gene ◽  
Connexin 26 ◽  
Common Mutation ◽  
Congenital Hearing Loss ◽  
35Delg Mutation ◽  
The Relationship

35delG is the most common mutation in the Connexin-26 gene, representing a major cause of autosomal recessive hearing loss. The aim of this study was to evaluate the relationship between the audiological phenotype and the 35delG mutation in 64 Sicilians with non-syndromic deafness. Pure-tone audiometry and a screening for 35delG mutation were performed. Audiograms were evaluated according to the classification of Liu and Xu. Thirteen homozygotes and nine heterozygotes for the investigated mutation were found. Symmetrical hearing loss was significantly (p=0.008) more common in homozygous subjects than in those without the Connexin-26 mutation. Profound-severe hypoacusia was found in 92.3 per cent of 35delG homozygous, 22.3 per cent of heterozygous and 58.7 per cent of 35delG absent patients. Residual shape audiograms were more frequent in homozygotes. A molecular analysis for the 35delG mutation should be performed in cases of symmetric, severe-profound congenital hearing loss, as a genetic cause is probable in such cases.

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.

Update of the spectrum of GJB2 gene mutations in 152 Moroccan families with autosomal recessive nonsyndromic hearing loss

2016 ◽  
Vol 59 (6-7) ◽  
pp. 325-329 ◽  
Author(s):  
Amina Bakhchane ◽  
Amale Bousfiha ◽  
Hicham Charoute ◽  
Sara Salime ◽  
Mustapha Detsouli ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Gjb2 Gene ◽  
Nonsyndromic Hearing Loss

Efficiency of SNPs for the Detection of 35DelG Mutation in 50 Cases with Nonsyndromic Hearing Loss

2018 ◽  
Vol 69 (8) ◽  
pp. 2273-2277
Author(s):  
Luminita Radulescu ◽  
Ghenadie Curocichin ◽  
Anastasia Buza ◽  
Sergiu Parii ◽  
Tatiana Meriacre ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensitivity And Specificity ◽  
Autosomal Recessive ◽  
Reference Method ◽  
Screening Tests ◽  
Gjb2 Gene ◽  
Single Nucleotide ◽  
Specificity And Sensitivity ◽  
Study Results ◽  
35Delg Mutation

Congenital sensorineural hearing loss (SNHL) is recognized as a major public health burden. Mutations in the GJB2 gene are among the most frequent encountered etiological factors (approximately 50% of cases of autosomal recessive sensorineural non-syndromic hearing loss in the Caucasian population). Single nucleotide polymorphisms (SNPs) are important markers in studies that correlate the genotype with the phenotype. The main purpose of the study is to develop and validate a molecular-genetic screening algorithm based on the SNP rs80338939 for later use in laboratories in Romania and the Republic of Moldova. A prospective study was conducted on 50 randomly included subjects with profound congenital SNHL. The 35delG mutation was assessed by two methods: a reference method (University Medical Center Freiburg, Germany) and the method to validate: single nucleotide polymorphism (SNP) for the same mutation. We compared the results of the two methods to assess the specificity and sensitivity of the method used in the study. Results obtained indicate a sensitivity of 92% and 98% specificity for the studied method when compared with the reference method. The high sensitivity and specificity of the proposed method confirms that rs80338939 can be used as a biomarker in the assessment of the risk of autosomal recessive SNHL. In fact, we aim to optimize the technique to achieve 100% sensitivity and specificity. At the same time, we acknowledge that the screening of 35delG mutations does not replace the audiological screening tests, because the auditory function involves 1% of the human genes and mutations of any of these may lead to deafness.

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