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

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.

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Genetics of non Syndromic Hearing Loss in the Republic of Macedonia

Balkan Journal of Medical Genetics ◽

10.2478/v10034-012-0020-0 ◽

2012 ◽

Vol 15 (Supplement) ◽

pp. 57-59 ◽

Cited By ~ 2

Author(s):

Emilija Sukarova Stefanovska ◽

D Plaseska Karanfilska ◽

M Cakar ◽

I Filipce

Keyword(s):

Hearing Loss ◽

Direct Sequencing ◽

Gene Mutations ◽

Developed Countries ◽

Deaf Children ◽

Mtdna Mutations ◽

Republic Of Macedonia ◽

Syndromic Hearing Loss ◽

The Republic ◽

Genetic And Environmental Factors

ABSTRACT Hearing impairment is the most common sensory deficit in humans affecting 1 in 1000 newborns. When present in an infant, deafness may have dramatic effects on language acquisition, seriously compromising the quality of their life. Deafness is influenced by both genetic and environmental factors, with inherited causes as the most prominent etiological factor in deafness in developed countries. The genetic basis of hearing loss is complex with numerous loci and genes underlying hereditary sensoryneural non syndromic hearing loss (NSHL) in humans. Despite the wide functional heterogeneity of the genes, mutations in the GJB2 gene are found to be the most common cause of sporadic and recessive NSHL in many populations worldwide. Molecular characterization of deafness in the Republic of Macedonia was performed in 130 NSHL profoundly deaf children from different ethnic origins. Molecular studies included direct sequencing of the GJB2 gene and specific polymerase chain reaction (PCR) analyses for the del(GJB6- D13S1830) mutation. Five common mitochondrial DNA (mtDNA) mutations [A1555G, 961delT+ C(n), T1095C, C1494T and A827G] were also analyzed using the SNaPShot method. In preliminary studies, GJB2 gene mutations were found in 36.4% of analyzed patients, with predominance of 35delG in Macedonian and Albanian patients and W24X in Gypsy patients, respectively. No del(GJB6- D13S1830) mutation was found. None of the analyzed deafness-associated mutations in mtDNA were identified in the studied patients

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

The Journal of Laryngology & Otology ◽

10.1017/s0022215108002892 ◽

2008 ◽

Vol 123 (3) ◽

pp. 273-277 ◽

Cited By ~ 5

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.

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Identification of both MT-RNR1 m.1555A>G and bi-allelic GJB2 mutations in probands with non-syndromic hearing loss

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2014.01.011 ◽

2014 ◽

Vol 78 (4) ◽

pp. 614-617 ◽

Cited By ~ 1

Author(s):

Yongchuan Chai ◽

Lianhua Sun ◽

Xiuhong Pang ◽

Xiaowen Wang ◽

Dongye Chen ◽

...

Keyword(s):

Hearing Loss ◽

Syndromic Hearing Loss ◽

Gjb2 Mutations

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Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India

Journal of Medical Genetics ◽

10.1136/jmg.40.5.e68 ◽

2003 ◽

Vol 40 (5) ◽

pp. 68e-68 ◽

Cited By ~ 70

Author(s):

M RamShankar

Keyword(s):

Hearing Loss ◽

Founder Effect ◽

Syndromic Hearing Loss ◽

Gjb2 Mutations

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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.

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Mutation Analysis of the Common Deafness Genes in Patients with Nonsyndromic Hearing Loss in Republic of Macedonia

Macedonian Medical Review ◽

10.1515/mmr-2017-0005 ◽

2017 ◽

Vol 71 (1) ◽

pp. 20-26

Author(s):

Emilija Sukarova Stefanovska ◽

Gjorgji Bozhinovski ◽

Ana Momirovska ◽

Marina Davceva Cakar ◽

Elena Sukarova-Angelovska ◽

...

Keyword(s):

Hearing Loss ◽

Modifier Gene ◽

Compound Heterozygous ◽

Nonsyndromic Hearing Loss ◽

Allelic Variants ◽

Republic Of Macedonia ◽

Pathogenic Variants ◽

Molecular Etiology ◽

The Common ◽

The Republic

Abstract Hearing impairment is the most common sensory disorder, which occurs in 1 of 1000 newborns. It is caused by heterogeneous conditions with more than a half due to genetic etiology. Although hundreds of genes are implicated in hearing process and have been found to be associated with nonsyndromic hearing loss, pathogenic variants in GJB2 gene have been considered as the main cause of deafness among nonsyndromic hearing loss (NSHL) population worldwide. Pathogenic variants in MT-RNR1 or mtDNA12SrRNA gene were also implicated predominantly in postlingual progresive deafness. The aim of this study was to analyze the implication of GJB2 and MT-RNR1 genes in the molecular etiology of deafness among 130 NSHL patients in the Republic of Macedonia. The presence of the del (GJB6-D13S1830) was also analysed. We performed SSCP and/or sequence analysis of GJB2 and identified sequence variants in 62 out of 130 patients (47.7%); (51 homozygous or compound heterozygous and 11 with only one variant allele). We found 8 different allelic variants, the most prevalent being c.35delG (65.49%), and p.W24*(23.01%), followed by other less frequent alleles (p.V27I, p.V37I, p. P175T and cd. delE120 or delGAG at 360). In addition, two polymorphic substitutions in the GJB2 gene with no clinical significance (p.V153I and p.R127H) were detected. No del(GJB6-D13S1830) was found. SNaPshot analysis was used to screen for the five most frequent allelic variants in the MT-RNR1 gene. Two MT-RNR1 mutations (A827G and T961G) were detected in three patients where only one GJB2 pathogenic variant was found. A new MT-RNR1 gene variant G1303A was also detected. In conclusion, MT-RNR1 mutations were not a significant contributor to the etiology of deafness in Macedonia, although could be considered as a modifier gene affecting the expression of deafness in patients carrying one GJB2 variant. On the other hand, the high percenttage of GJB2 pathogenic variants identified among NSHL cases indicates the necessity of molecular newborn screening for the two most common GJB2 variants (c.35delG and p.W24*) in the Republic of Macedonia.

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Connexin 26 and 30 mutations in paediatric patients with congenital, non-syndromic hearing loss treated with cochlear implantation in Mediterranean Turkey

The Journal of Laryngology & Otology ◽

10.1017/s0022215112002587 ◽

2012 ◽

Vol 127 (1) ◽

pp. 33-37 ◽

Cited By ~ 8

Author(s):

Ö Tarkan ◽

P Sari ◽

O Demirhan ◽

M Kiroğlu ◽

Ü Tuncer ◽

...

Keyword(s):

Hearing Loss ◽

Cochlear Implantation ◽

Autosomal Recessive ◽

Connexin 26 ◽

Enzyme Linked Immunosorbent Assay ◽

Paediatric Patients ◽

Study Population ◽

Connexin 30 ◽

Syndromic Hearing Loss ◽

35Delg Mutation

AbstractObjective:Mutations in the genes for connexin 26 (GJB2) and connexin 30 (GJB6) play an important role in autosomal recessive, non-syndromic hearing loss. This study aimed to detect the 35delG and 167delT mutations of theGJB2gene and the del(GJB6-D13S1830) mutation of theGJB6gene in paediatric patients diagnosed with congenital, non-syndromic hearing loss and treated with cochlear implantation in Mediterranean Turkey.Materials and method:We included 94 children diagnosed with congenital, non-syndromic hearing loss and treated with cochlear implantation. Blood samples were collected, DNA extracted and an enzyme-linked immunosorbent assay performed to enable molecular diagnosis of mutations.Results:Of the 94 children analysed, the 35delG mutation was detected in 12 (12.7 per cent): 10 (83.3 per cent) were homozygous and 2 (16.7 per cent) heterozygous mutant. The 167delT and del(GJB6-D13S1830) mutations were not detected.Conclusion:The GJB2-35delG mutation is a major cause of congenital, non-syndromic hearing loss in this study population.

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