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

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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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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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.

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