Haplotype Analysis of Seven Non-Syndromeic Autosomal Recessive Hearing Loss Loci in Iranian Families

Objective: Hearing impairment is the most frequent sensorineural defect in 2 forms, syndromic and non–syndromic. The aim of this study is haplotype analysis of seven loci of non–syndromic autosomal recessive hearing loss in Iranian families. Materials & Methods: In this descriptive study, forty one Iranian families with 2 or more affected individuals segregating as an autosomal recessive non–syndromic hearing loss were selected simply and conveniently. The patients have been tested negative for the following loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB6, DFNB7/11, DFNB8/10, DFNB9, DFNB12, DFNB16, DFNB18, DFNB21, DFNB23, DFNB29 and DFNB4 previously. The subjects have been investigated additional 7 loci (DFNB22, DFNB28, DFNB30, DFNB31, DFNB36, DFNB37 and DFNB67) , to determine the prevalence of these genes involve in these loci. Homozygosity mapping was applied using number of STR (Short Tandem Repeat) markers. Results: Three families linked to the following loci DFNB28, DFNB30 and DFNB 31. Conclusion: In this research, the cause of additional 7% of non–syndromic hearing loss was determined in Iranian population

Association of Polymorphisms at LDLR Locus with Coronary Artery Disease Independently from Lipid Profile

Coronary artery disease (CAD) is the leading cause of mortality in many parts of the world. Genome-wide association studies (GWAS) have identified several genetic variants associated with CAD in Low-density lipoprotein receptor (LDLR) locus. This study was evaluated the possible association of genetic markers at LDLR locus with CAD irrespective to lipid profile and as well as the association of these SNPs with severity of CAD in Iranian population. Sequencing of 2 exons in LDLR gene (Exon 2, 12) and part of intron 30 of SMARCA4 gene include rs1122608, was performed in 170 Iranian patients angiographically confirmed CAD and 104 healthy controls by direct sequencing. Sullivan's scoring system was used for determining the severity of CAD in cases. Our results showed that homozygote genotypes of rs1122608 (P<0.0001), rs4300767 (P<0.005) and rs10417578 (p<0.007) SNPs have strong protective effects on the CAD. In addition, we found that rs1122608 (GT or TT) was at higher risk of three vessel involvement compared to single vessels affecting (P=0.01)

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

Exome sequencing utility in defining the genetic landscape of hearing loss and novel-gene discovery in Iran

Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non-syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease-causing variants in known deafness-associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness-associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30% of our study cohort using ES. This study corroborates the observation that high-throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL