Mutation analysis of connexin 26 gene and del (GJB6-D13S1830) in patients with hereditary deafness from two provinces in Iran

Mutations in the connexin 26 (Cx26) gene at the DFNB1 locus on chromosome 13q12 are associated with autosomal recessive non-syndromic hearing loss (ARNSHL). There are many known mutations in this gene that cause hearing loss. A single frameshift, at position 35 (35delG) accounts for 50% of mutations in the Caucasian population with carrier frequencies of 1.5-2.5%. In this study we investigated the prevalence of Cx26 gene mutations by directly sequencing the coding exon of this gene belonging to ARNSHL individuals from 53 families in Qom and Markazi provinces of Iran. Seven different Cx26 variants were identified. Five Cx26 mutations including 35delG, 233delC, 176del16, W24X, L90P were found in 10 of 53 families (18.87%). One olymorphism V153I was also found. One variant A171T with unknown effects was also detected. Six of the 53 families were observed to have GJB2 mutations in both alleles (11.32%). The most common mutation was 35delG. Three out of 10 families (30%) with GJB2 variants contained 35delG mutation in both alleles and the frequency of 35delG allele was 0.50 among 10 out of 53 families. Also screening for the 342-kb GJB6 deletion mutant did not reveal any large deletion among families studied. Thus, in the two provinces, contribution of GJB2 (Gap Junction Protein Beta 2) mutations to familial deafness appears to be less significant. This necessitates further assessment of the other known genes regions as well as a search for new genetic factors in hereditary deafness in the Iranian population

Contribution of GJB2 mutations and Four common DFNB loci in autosomal recessive non-syndromic hearing impairment in Markazi and Qom provinces of Iran

This study aimed to investigate the contribution of four common DFNB ("DFN" for deafness and "B" for autosomal resessive locus) loci and GJB2 gene mutations (exon 2) in hearing impairment in individuals living in Markazi and Qom provinces of Iran. Forty consanguineous Iranian families with at least three affected individuals in family or pedigree who suffer from an autosomal recessive non-syndromic congenital hearing impairment were the subjects of this study. Blood samples were taken from both hearing and non-hearing individuals, DNA was extracted and amplified by using specific primers for the coding region of GJB2 gene (exon 2). The PCR product of GJB2 gene was then sequenced. Also short tandem repeat (STR) markers amplified by using specific primers for loci DFNB2, DFNB3, DFNB4 and DFNB21. At least 2 microsatellite markers (STR) for each DFNB locus exceeding to 4-6 markers for the linked families were used. The amplified markers were analyzed by conventional Polyacrylamide Gel Electrophoresis followed by silver staining. Six families were homozygous or compound heterozygous for GJB2 mutations and were excluded from further studies. Linkage analysis was carried out for the remaining 34 families by genotyping the flanked STR markers of DFNB2, DFNB3, DFNB4 and DFNB21 loci. Six families showed linkage; including one family to DFNB2, two families to DFNB3 and three families to DFNB4 locus while no family showed linkage to DFNB21 locus. Undoubtedly, the best understanding of the genetic basis of hearing loss in Iranian population will be achieved by performing similar experiments in other provinces and also by analyzing more loci

Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss

Background: Hearing loss (HL) is the most frequent sensory birth defect in humans. Autosomal recessive non-syndromic HL (ARNSHL) is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB) have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families. Methods: Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with >= 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then subjected to homozygosity mapping for fifteen ARNSHL loci. Results: Sixteen families were found to be linked to seven different known loci, including DFNB I (6 families), DFNB4 (3 families +1 family with Pendred syndrome), DFNB63 (2 families), DFNB2 (1 family), DFNB7/11 (1 family), DFNB9 (1 family) and DFNB21 (1 family). DNA sequencing of the corresponding genes is in progress to identify the pathogenic mutations. Conclusion: The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investigations will have to be done to reveal the causes in the remaining families

Accessing Genetic and Environmental Factors of Hearing Loss in 354 Families in Gom and Markazi Provinces

Objective: Hearing loss (HL) is the most prevalent sensorineural defect in human. Mild to severly Profound HL occurs in about l.0 per 1000 births. Many previous studies have shown that about 50% of deafness is due to genetic factor and 50% is due to environmental and etiologically unknown. In this study, we are searching the causes of deafness at these families and introduce strategies for diagnosis and prevention. Materials & Methods: Questionaires were distributed in deaf schools, hearing loss and rehabilitation centers in Qom and Markazi provinces collecting done after filling by the parents. The criterias such as age, sex, number of deaf individuals in families their close relatives, the marriage type of the parents and etiology of disease (if it is genetic or environmental) were extracted from questionnaires and were analysed by SPSS software. Results: Three hundred and fifty four (354) Questionnaires contained complete information from hearing loss families were collected. Age mean of proband individuals is 16.1±8.1. Sex distribution of 48.4% and 51.6% girls and boys, respectively. Parents were 59.3% and 36.7% of consanguineous and unfamilial marriage, respectively. The marriage type of were not determined in 4%. Mean of deaf individuals among these families was 1.8±1.4.By assessing the filled questionnaires and pedigrees. The deafness etiology in the studies population was categorized as genetic cause (70.9 %), environment factor (9%) and unknown etiology (20.1%). Conclusion: Genetic factor with and autosomal recessive inheritance pattern was the most common cause of hearing loss due to the high prevalence of consanguineous marriage which resulted and increased genetic causes in more than 50%. Multiplicity of offspring also shawn an increased in frequency of hearing loss in families that have deaf with genetic background of this disorder. In this study, environmental and unknown factors are second cause of HL. We may interestingly reduce frequency of HL in Iran with discouraging consanguineous marriage, health education, population regeneration control also genetic counseling especially for high risk families

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Abstract Mutations in the connexi

Preclinical tumor mouse models for studying esophageal cancer

Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer. In this review, we have elucidated the production and usage of current mouse models, such as xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), for studying esophageal cancer. Additionally, we have briefly discussed various gene-editing tools that could potentially be employed in the future to create mouse models specifically for esophageal cancer research.</p

Preclinical tumor mouse models for studying esophageal cancer

Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer. In this review, we have elucidated the production and usage of current mouse models, such as xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), for studying esophageal cancer. Additionally, we have briefly discussed various gene-editing tools that could potentially be employed in the future to create mouse models specifically for esophageal cancer research.</p