Progress of Education, Research and Services in Medical Genetics, in Some Institutions of Iran

The present paper is a review of progress and major activities in education, research, services and ethics in the field of medical genetics in some centers in Iran. National projects of population genetics, genetic epidemiology, like national human genome projects, Connexin 26 and Pejvakin, distribution of thalassemia, hemophilia, etc in different ethnic groups, and religious minorities of Iran, are mentioned

Report of a new mutation and frequency of connexin 26 gene (GJB2) mutations in patients from three provinces of Iran

Autosomal recessive and sporadic non-syndromic hearing loss (ARSNSHL) is the major form of hereditary deafness. Mutations in the GJB2 gene encoding the gap-junction protein Connexin 26 have been identified to be highly associated with ARSNSHL. In this study we have analyzed 196 deaf subjects from 179 families having one or more deaf children in 3 proviences of Iran, including Kordestan, Khuzestan and Golestan. The nested PCR prescreening strategy and direct sequencing technique were used to detect the mutations in coding exon of the gene. Altogether 3 GJB2 recessive mutations including 35delG, 167delT and V27I+E114G, were identified in 23 of 179 families (12.8). Fourteen of 179 families were observed to have GJB2 mutation in both alleles (7.8). A novel variant (R159H) also was found in a deaf family from Khuzestan. Four polymorphisms V27I, E114G, S86T and V153 I also were detected in 7 families. A polymorphism(S86T) was seen in the whole population studied. Our data indicated that the rate of connexin 26 mutations is different in this three Irainian population and is lower than the high frequency of 35delG (26) reported from Gilan province in the north of Iran

Frequency of a very rare 35delG mutation in two ethnic groups of Iranian populations

The 35delG mutation in the Connexin 26 gene (Cx26), at the DNFB1 locus is the most common mutation in the patients with autosomal recessive non-syndromic hearing loss (ARNSHL). We have studied a total of 224 deaf cases from 189 families in two populations of Iran (Sistan va Bluchestan and Hormozgan provinces) by prescreening nested PCR, polyacrylamide gel electrophoresis and consequent direct sequencing method for all cases. The aim of the present work was to find prevalence of GJB2 mutations in the populations studied. Four different GJB2 mutations including 35delG, W24X, R127H and (V27I + E114 G) were identified in 11 of 189 families (5.8). Two polymorphisms (V27I and V153I) also were detected in 14 families. A polymorphism S86T was determined in all cases. Homozygote 35delG mutation was found only in 1 of 189 families (0.5).The rate of Cx26 mutations found in this study was lower than other Iranian populations. So the cause of deafness in the populations studied remains to be detected in other loci or genes. © 2014, Iranian Journal of Public Health. All rights reserved

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

Molecular pathology of 6 novel GJB2 allelic variants detected in familial and sporadic Iranian non syndromic hearing loss cases

Background: Mutations of GJB2 gene encoding connexion 26 are the most common cause of hearing loss in many populations. A very wide spectrum of GJB2 gene mutations associated with hearing loss have been detected but pathogenic role has been tested only for a part of them. In this study, we have provided genetic evidence on the pathogenicity of our previously reported novel GJB2 allelic variants. Methods: The pathogenic role of GJB2 allelic variants were assessed using co segregation of each allelic variant with hearing loss in family members, absence of the allelic variants in control populations, coexistence with a second GJB2 mutation, nature of the amino acid substitution and evolutionary conservation of the appropriate amino acid. Results: The GJB2 allelic variants including 363delC, 327delGGinsA, H16R and G200R have been co segregated with autosomal recessive non syndromic hearing loss in five families and are not found in control subjects. The G130V and K102Q were found in heterozygous state in two deaf individuals. G130V results in an exchange a residue highly conserved among all the connexins but was found with a rate of 1% in control subjects and K102Q results in an exchange a residue not conserved among all the connexins and not identified in control subjects. Conclusion: We conclude that, 363delC, 327delGGinsA, H16R and G200R may be pathogenic. However, the pathogenicity and inheritance of K102Q and G130V can not be assessed clearly and remains to be identified

Molecular detection of prostate specific antigen in patients with prostate cancer or benign prostate hyperplasia the first investigation from Iran

Prostate cancer is the second common form of cancer in men. Detection of circulating Prostate Specific Antigen (PSA) transcripts has effectively been used for early diagnosis of prostate cancer cells. This investigation employed a reverse transcriptase polymerase chain reaction (RT-PCR) technique to distinguish the patients with either localized or metastatic prostate cancer (CaP) vs. Benign Prostate Hyperplasia (BPH) and control subjects, as compared with clinical and pathological records. With reservation of ethical issues, blood samples were collected from 60 cases. Based on pathological and clinical findings, 25 patients (20 with localized cancer, 5 with metastatic), 22 with BPH, and 13 healthy (including 3 females) subjects as negative controls, were selected from Shariati, Mehrad, Sina,, Khatam and Atie Hospitals in Tehran, Iran. RT-PCR for a 260 bp PSA transcript was then performed. Clinical and pathological records were used for the assessment and comparison of PSA RT-PCR results. None of the control subjects and BPH (with 7 exceptions) were found positive by RT-PCR (Relative specificity= 72.7). In patients with prostate cancer, 21 out of 25 were found PSA positive (Relative sensitivity= 83.4) and the remaining 3 have been shown to be PSA negative (Positive predictive value= 83.4). All of 5 metastatic patients (100) revealed PSA positive results. Our data reflects the clinical relevance and significance of RT-PCR results as assessed with clinical and pathological examinations. PSA RT-PCR might be used as a powerful means for diagnosis, even when either pathological or clinical findings are negative, and could be employed for further molecular epidemiology surveys