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

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.

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

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.

Genetic Screening for 35delG Mutation in Egyptian Patients with Profound Sensorineural Hearing Loss Scheduled for Cochlear Implantation: A Population-Based Study

<b><i>Objectives:</i></b> The aim of this work was to assess the type and site of the 35delG gene mutation in patients presenting with profound SNHL and scheduled for cochlear implantation. The secondary objectives were to determine their geographical distribution throughout Egypt, screening of the parents for the mutation, and to correlate the type of mutation with clinical severity and outcomes after surgery. <b><i>Methods:</i></b> The study was carried out on 100 consecutive patients scheduled for cochlear implantation. Patients with syndromic hearing loss or noncongenital hearing loss (trauma, infections, and ototoxicity) were excluded. All patients were subjected to detailed history taking including geographic tagging for their origins in Egypt, imaging (CT and MRI cochlear implantation protocols), full audiological evaluation (PTA, ABR, and TEOAE), and genetic screening for GJB2 mutation using Invitrogen PCR mix and ApaI restriction enzyme (North America, CA, 10572-014). The parents of mutation-positive patients were also subjected to audiological and genetic analysis. All patients were subjected to postimplantation evaluation of hearing after 6 and 12 months. <b><i>Results:</i></b> There were 64 males and 36 females from 98 families. Ages ranged between 1.9 and 7 years (mean 3.72 years). They originated from all over Egypt but the majority came from the Giza and Cairo areas. The 35delG mutations were found in exon 2 in 31% of the cases and all were heterozygous. In the parents, 18 mothers and 13 fathers were positive but only 8 had mild to moderate SNHL. Hearing evaluation by pure tone and speech discrimination scores at 6 and 12 months showed that the 35delG children had a statistically better result compared to the children without this mutation. <b><i>Conclusion:</i></b> The prevalence of the 35delG mutation in nonsyndromic children in this sample was 31% which is different from previous studies in the Egyptian population but close to the values found in other populations in the Mediterranean basin.

Mutations in the gjb2 gene in children with bilateral hearing loss in Kyrgyzstan

The purpose of this work was to identify and study the prevalence of mutations in the GJB2 gene encoding the connexin 26 protein in the Kyrgyz Republic. Hearing loss is currently the most widespread disease. This paper presents a study of 89 patients with persistent bilateral sensorineural hearing loss and deafness of unknown etiology. All patients were divided into two groups. One group included patients with an unburdened family history, the second group included patients with a burdened family history. When clarifying the etiology of the disease, we can assume further dynamics of the hearing thresholds, as well as select the necessary tactics for managing such patients for early rehabilitation. As a result of molecular genetic research, mutations in the GJB2 gene were detected in 19 patients (21,3%). The 35delG mutation was found in a homozygous state in 5 children from parents of Russian and Tatar origin. In 4 families, parents were in an assorted marriage. Among 62 Kyrgyz, mutations in the GJB2 gene were detected in 9 cases, which accounted for 14,5% of cases. The 35delG mutation among the Kyrgyz was found only in the compound heterozygous state with the 235delC mutation in 3 children and with the –23 + 1G> A mutation in one child.

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

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.

Frequency of c.35delG Mutation in GJB2 Gene (Connexin 26) in Syrian Patients with Nonsyndromic Hearing Impairment

Background. Hearing impairments (HI) are the most common birth defect worldwide. Very large numbers of genes have been identified but the most profound is GJB2. The clinical interest regarding this gene is very pronounced due to its high carrier frequency (0.5–5.4%) across different ethnic groups. This study aimed to determine the prevalence of common GJB2 mutations in Syrian patients with profound sensorineural HI. Methods. We carried out PCR, restriction enzyme based screening, and sequencing of 132 Syrian patients diagnosed clinically with hereditary deafness for different GJB2 mutations. Results. The result revealed that, in GJB2 gene, c.35delG is the most prevalent among affected studied subjects (13.64%), followed by c.457G>A (2.4%). Conclusion. The benefit of this study on the one hand is its first report of prelingual deafness causative gene mutations identified by sequencing technology in the Syrian families. It is obvious from the results that the deployment in biomedical research is highly effective and has a great impact on the ability to uncover the cause of genetic variation in different genetic diseases.

Hearing Function in Heterozygous Carriers of a Pathogenic GJB2 Gene Mutation

The most frequent hereditary hearing loss is caused by mutations in the GJB2 gene coding for the gap junction beta 2 protein Connexin 26 (Cx26). In contrast to many studies performed in patients with bi-allelic mutations, audiometric studies on heterozygotes are sparse and often contradictory. To evaluate hearing function in heterozygous carriers of the GJB2 c.35delG mutation, audiometry over the extended frequency range and the recording of otoacoustic emissions (OAEs), i.e., transient-evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs), were performed in a group of parents and grandparents of deaf children homozygous for the GJB2 c.35delG mutation. The comparison of audiograms between control and heterozygous subjects was enabled using audiogram normalization for age and sex. Hearing loss, estimated with this procedure, was found to be significantly larger in GJB2 c.35delG heterozygous females in comparison with controls for the frequencies of 8-16 kHz; the deterioration of hearing in heterozygous men in comparison with controls was not statisticaly significant. A comparison of TEOAE responses and DPOAE levels between GJB2 c.35delG heterozygotes and controls did not reveal any significant differences. The results prove the importance of using audiometry over the extended frequency range and audiogram normalization for age and sex to detect minor hearing impairments, even in a relatively small group of subjects of different ages.