Screening of Autosomal Recessive Non-Syndromic Hearing Loss gor GJB2 Mutations

Objective: Hereditary Hearing loss (HHL) affects one in 1000-2000 newborns and more than 50% of these cases, the loss has a genetic basis. About 70% of HHL is non-syndromic with autosomal recessive forms accounting for ~85% of the genetic load. To date, more than 100 locus estimated for this kind of deafness. Different genes have been reported to be involved, but mutations in the connexin 26 gene (Cx26) have been established as the basis of autosomal recessive non-syndromic hearing loss. The aim of this project is to study the prevalence of connexin 26 mutations. Materials & Methods: In this descriptive study, the prevalence of connexin 26 mutations was evaluated by using amplification refractory mutation system (ARMS)-PCR for detection of 35delG and then analyzed all samples excluding 35delG homozygote by DHPLC and direct sequencing. 38 patients with autosomal recessive non-syndromic hearing loss were selected simply and participated in this research.  Results:  76 chromosomes (38 patient) were screened for GJB2 mutations. Thirty two (42%) carry GJB2 mutations including 35 delG, W24X, R32H, R127H, -3170G>A. Among them, 35 delG has the highest frequency (84%). Polymorphism V153I was found in three chromosomes. Conclusion: According to these results, other loci and genes may be the major responsible for nonsyndromic deafness in this population

Linkage Analysis for 50 Iranian Families with Autosomal Recessive Non-Syndromic Hearing Loss for DFNB21 Locus

Objective: Congenital hearing loss occurs in 1 out of 1000 births and about 50% of all cases are estimated to be of genetic origin. About 70% of hereditary hearing loss is non-syndromic with autosomal recessive inheritance accounting for 80% of the genetic load. To assess the importance of other loci in the Iranian population, we screened 50 consanguineous families with ARNSHL for DFNB21, which was linked to ARNSHL in Middle East countries.  Materials & Methods: 50 consanguineous families with at least three affected children, previously excluded by mutational analysis from GJB2 and GJB6 genes, were included in this study. We used three polymorphic markers including D11S1998, D11S4464, and D11S1299 in this study. Results: Two families were linked to DFNB21 and two novel mutations have been detected so far. In two families a 266 Del T mutation and a large 9611bp deletion that starts from intron 9 and includes exon 10 in TECTA gene were detected. Conclusion: This study showed that mutations in DFNB21 locus are the most common cause of ARNSHL in Iranian population. It seems that DFNB21 may play an important role in genetic load of ARNSHL in Iran. This will be confirmed by screening more families for this locus in Iranian deaf population

Prevalence Study of GJB2 Gene Mutations in Iranian Ethnics

Objective: Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and deletion in a portion of GJB6 to the autosomal recessive non-syndromic deafness genetic load in Iran. Materials & Methods: In this descriptive and cross – sectional study1605 probands from 1605 different nuclear families with autosomal recessive non-syndromic hearing loss were investigated. Hearing loss tests and clinical examination were done and 10 ml blood was drawn as DNA source. After study of 35delG mutation by ARMs PCR, negative or heterozygote individuals were sent to IOWA University for detection of other GJB2 mutations.  Results: GJB2-related deafness was found in 243 families (15.1%). Conclusion: Varient geographic pattern for GJB2-related deafness has considerable results in Iran in comparable with other study in Europe and our neighboring countries and deletion in GJB6. [∆ (GJB6-D13S1830)] hasn't been detected in our studied population