Familial and sporadic GJB2-related deafness in Iran: review of gene mutations

Mutations in the GJB2 gene encoding connexin 26 protein, are the main cause for autosomal recessive and sporadic non syndromic hearing loss in many populations. Here, we have taken together and reviewed results from our six previous publications, our unpublished data from ten Iranian provinces, as well as data from two previous mutation reports to provide a comprehensive collection of data for GJB2 mutations and deafness in Iran. In all, 1095 hearing impaired students and their deaf siblings from 890 families in 10 provinces of Iran were studied. The prevalence and type of the GJB2 gene mutations were investigated using nested PCR pre screening strategy and direct sequencing of the coding exon of the gene. Altogether 31 different genetic variants were detected from which 17 GJB2 mutations were identified. GJB2 mutations were found in 14.6% of deaf families [18.29% of familial and 12.7% of sporadic cases]. We found GJB2 mutations in both alleles in 78% of GJB2 mutations chromosomes. However, 35delG mutation was the most common GJB2 mutation accounting for 74.5% of the mutations in populations studied. Our data indicated that a specific combination of GJB2 mutations types and frequencies was presented in different populations of Iran. These results also highlight the importance of GJB2 mutations in development of hearing loss in familial and sporadic deaf families in different parts of the country and can be used as a basis of genetic counseling and clinical guideline in Iran

Autosomal recessive and sporadic non syndromic hearing loss and the incidence of Cx26 mutations in a Province of Iran

Despite the enormous heterogeneity of genetic hearing loss, mutations in the GJB2 [connexin 26] gene located on 'DFNB1' locus [13q12] account for up to 50% of cases of autosomal recessive non-syndromic hearing loss [ARNSHL] in some populations. This study describes the analysis of 100 autosomal recessive and sporadic nonsyndromic hearing loss individuals from 79 families each having at least one deaf child in Chehar Mahal va Bakhtiari province in west of Iran. We have investigated the prevalence of the connexin 26 gene mutations using nested PCR strategy to screen the predominant 35delG mutation and subsequent direct sequencing to detect other Cx26 mutations. Seven different genetic variants were detected from which one novel variant was including 363delC. The 35delG was the most common mutation found in 5 of 79 families [6.3%]. Cx26 related deafness mutations [35delG, [V27I; E114G]] and R127H] were found in 12 of 158 chromosomes studied [7.8%]. We conclude that the association of Cx26 mutations with deafness in Chehar Mahal va Bakhtiari province is low and looks like most other populations of Iran

Frequencies of mutations in the connexin 26 gene [GJB2] in two populations of Iran [Tehran and Tabriz]

While hearing loss has been considered to be a very heterogeneous disorder, mutations in Gap junction beta 2 [GJB2] gene encoding Connexin 26 [Cx26] protein are the major cause of autosomal recessive and sporadic non-syndromic deafness in many populations. In this study, we have investigated the prevalence of the GJB2 gene mutations using nested PCR pre screening strategy and direct sequencing method. Two hundred and seventy two hearing impaired subjects were studied from 210 families obtained from two large cities of Iran [Tehran and Tabriz]. Twenty four different genetic variants were identified. Cx26 mutations were found in 53 of the 210 families [25.2%] including T8M, 35delG, W24X, R32H, V37I, E47X, 167delT, delE120, Y136X, R143W, R184P, 235delC and V27I+E114G. Homozygosity and compound heterozygosity for the Cx26 mutations were found in 39 of 210 [18.5%] families. Homozygosity for the 35delG mutation was the most common that causes hearing loss in 28 [13.3%] patients. Six novel variants H16R, E101E, K102Q, G200R, 327delG and G130A were detected in this study. As a conclusion, the present survey revealed that the rate of mutation in Cx26 gene in our area is lower than in Europe; nevertheless, this rate is regarded as a considerable cause of deafness in the cited provinces in Iran