[Screening of DFNB4 locus in Iranian families with hereditary hearing impairment]

Mutations in the SLC26A4 gene in the DFNB4 locus is responsible for syndromic [Pendred syndrome] and non-syndromic hereditary hearing loss [HHL]. In many populations, mutations in this gene have been reported as a second cause of HHL. The objective of this study was to investigate the prevalence of SLC26A4 mutations in our HHL consanguineous families. After completing clinical evaluation and obtaining signed consent forms from each family, we included 80 families with two or more affected individuals, referred to the Genetics Research Center [GRC]. All families that previously tested negative for the DFNB1 locus were candidates for homozygosity mapping using STRs for DFNB4 locus. Families localized to this region were subjected to complete DMA sequencing. Twelve out of 80 families were mapped to DFNB4. Sequence analysis of 12 linked families revealed 10 mutations in 8 families. [T420I, 1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA, and L445W]. The T420I, G334V, L597S and R79X were novel mutations; we did not find any mutation in the four linked families, nor did we detect any nonsyndromic families with mutation in the SLC26A4 gene. We have been able to identify mutation in the SLC26A4 gene in only 8 of 80 families. In 12 families, we detected some degree of diffuse or nodular goiter; three out of 12 families showed thyroid function impairment and in five of 12 families there were positive prechlorate discharge tests. Eight families that showed mutation had normal temporal bone scan. This investigation, demonstrated that the SLC26A4 gene mutation is the most prevalent syndromic hereditary hearing loss in Iran, a finding in accordance with reports from other countries

[Spectrum of GJB2 gene mutations in nonsyndromic autosomal recessive deaf patients in Yazd]

Hearing loss is the most common sensory neural defect in humans, affecting 1 in 1000 neonates, with over half of these cases predicted to be hereditary in nature. Most hereditary hearing loss is inherited in a recessive fashion, accounting for approximately 80% of non-syndromic hearing loss [NSHL]. Mutations in GJB2 gene are major cause of inherited deafness in the European and American populations. To date, more than 90 mutations have been reported in this gene. Although most of these mutations are rare but 35delG mutation is the most common deafness causing allelic variant of GJB2 in most parts of t he world. In this project, 120 probands from 120 families with ARNSHL in Yazd Province were studied. Mutations Screening of GJB2 was performed by Amplification Refractory Mutation System [ARMS]-PCR for detection of 35delG and then all samples excluding 35delG homozygote were analyzed by DHPLC and Direct Sequencing. GJB2-related deafness was present in 7.5% of this population. We identified 4 mutations [35delG, 312del14, 314del14 and 167delT] and 4 polymorphisms [V153I, V27I, E114G and R127H] in this study. Prevalence of GJB2 mutations in this population was lower than American and European populations, and also other provinces of Iran. Interestingly, 312del14 rather than 35delG was the most common mutation found in the population under study. 56.25% of GJB2 mutant alleles carried 312del14 mutation. To date, this frequency has not been reported in any of the world populations

[Relative frequency of 35delG mutation in GJB2 gene in autosomal recessive non-syndromic hearing loss [ARNSHL] patients in Kerman population]

Congenital hearing loss with many genetic and environmental causes affects 1 in 1000 newborns. Mutations in the GJB2 [Gap Junction Beta-2] gene encoding the gap junction protein connexin 26 have been established as the main cause of autosomal recessive non-syndromic hearing loss. The aim of this stand was to study the frequency of one mutation [35delG] of GJB2 gene in Kerman non-syndromic deaf population. For this purpose, 130 chromosomes from 65 patients were studied and 35delG mutation was diagnosed in 3 [2.3%] chromosomes [one patient was homozygote and the other one was heterozygote]. This rate of frequency is significantly higher comparing to that in the whole population of Iran