Genetic linkage analysis of 15 DFNB loci in a group of Iranian families with autosomal recessive hearing loss

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. 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. Sixteen families were found to be linked to seven different known loci, including DFNB1 [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. 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

[Offering a proper framework to investigate water quality of the Atrak river]

The Atrak River is an important water supply resource in the Razavi Khorasan, Northern Khorasan and Golestan provinces. This river is the line border of Iran and Turkistan countries. Unfortunately, lack of water quality and quantity data due to nonexistence of a proper surface water quality monitoring station network is one of themain problems for water quality evaluation in the Atrak River. The main objective of the research is to offer a proper framework for surface water quality evaluation regarding to the mentioned limitations. In the first step, proper surface water quality monitoring stations along Atrak River are selected and water quality conditions are indicated using water quality index [WQI] model. The second step is allocated for determining trophic states of the river. Finally, the river water quality modeling is carried out for one of the most important index of water quality in the Atrak River i.e. total dissolved solids [TDS] based on proposed method by Oconnor [1976]. Results of WQI model showed that most of the stations were in the moderate class. The result also showed that most parts of this river had trophic condition. Finally, based on findings of O'Conor model it is demonstrated that the salinity status observed in these four stations originated from the base flow and therefore, salinity is affected by the natural sources. This methodology in the research can be used in rivers which don't have the proper surface water quality monitoring stations and therefore encountered with lack of water quality data. It can provide the proper strategy and management tasks to reach the good water quality conditions

Molecular genetics, diagnosis and treatment of breast cancer: review article

Breast cancer is the most common cancer among women, and one out of 8 or 10 women is diagnosed with breast cancer. This type of cancer is an extremely heterogenous disease, which is classified into multiple categories including LCIS [Lobular carcinoma in situ], DCIS [Ductal carcinoma in situ], and invasive carcinoma. BRCA1 and BRCA2 are two major high-risk genes associated with hereditary breast cancer. Mutations in CHEK2 gene also contribute to a substantial fraction of familial breast cancer. Susceptibility alleles in other genes are also rare causes of breast cancer. More than 1000 mutations have been identified in BRCA1 and BRCA2, and molecular assays for detecting mutations in these genes are now well established. Mutations in BRCA1 and BRCA2 cause genomic instability, which leads to alterations in additional key genes including tumor suppressor genes and/or oncogenes

There is a promise of tailoring treatment programs for individual women in near future. The emergence of miRNAs as regulators of gene expression identifies them as a novel candidate for diagnostic and prognostic indicators and therapeutic targets. The ability of miRNAs to simultaneously regulates many target genes and makes them attractive candidates for regulating stem cell self-renewal and cell fate decisions. The involvement of miRNAs in the initiation and progression of human malignancy holds much potential for new developments in current diagnostic and therapeutic strategies in the management of patients with breast cancer. The identification of novel miRNAs, the elucidation of their mRNA targets, and an understanding of their functional effects will improve our knowledge of the roles of these novel biomarkers in carcinogenesis, including breast cancer, and open avenues for potential therapeutic intervention

[Mutation screening of GJB2 and GJB6 and genetic linkage study of three prevalent DFNB loci in Iranian families with autosomal recessive non-syndromic hearing loss]

The incidence of prelingual hearing loss [HL] is about 1 in 1000 neonates of which, more than 60% of cases are inherited. Non-syndromic HL [NSHL] is extremely heterogeneous: more than 100 loci have been identified. The most common form of NSHL is the autosomal recessive form [ARNSHL]. Here, we have investigated CX26 [GJB2] and CX30 [GJB6] gene mutation and linkage analysis of 3 known loci in Iranian families. A cohort of 36 big ARNSHL pedigrees from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 [del D13S1830 and del D13S1854] mutations using direct sequencing and multiplex PCR, respectively. The negative mutations pedigrees for the above-mentioned mutations, were then tested for the linkage to the 3 known loci, including DFNB3[MYO7A], DFNB4[SLC26A4] and DFNB7/11[TMC1], using STR markers and conventional PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4 and 1 family was linked to DFNB7/11. DFNB1 [GJB2] and DFNB4 are the main causes of ARNSHL in our study samples and GJB6 mutations are apparently absent in the Iranian population

Microdeletion study in children with selective congenital heart disease; an Iranian multicenter study

Determining the frequency of chromosome 22q11.2 microdeletion in children with congenital cardiac conotruncal abnormalities using Fluorescence in-situ Hybridization [FISH] technique and estimating relation between DiGeorge Syndrome and cardiac conotruncal abnormalities. One-hundred and eighty cases [106 Males, 74 Females] with selective congenital heart disease [conotruncal abnormalities] referred to the hospitals affiliated to Tehran University during 2004-2007 were evaluated by pediatric cardiologists. All patients were assessed for chromosome 22q11.2 microdeletion using FISH technique. Consequently, patients with 22q microdeletion were studied for T cell abnormalities. Median age of the patients at the time of study was 18 months [3d-16y]. The microdeletion of chromosome 22q11.2 was detected in 17 [9.5%] patients with conotruncal abnormalities, including 5 [29.4%] Tetralogy of Fallot plus Supravalvular Pulmonary Stenosis, 4 [23%] Truncus Arteriosus, 5 [29.4%] Pulmonary Artesia with Ventricular Septal Defect, 2 [11.8%] CO AO+Intrrupted Aortic Arch and one case of Valvular Pulmonary Stenosis. Five of uncorrelated cases had crananiofacial dysmorphism. Chromosome 22q11.2 microdeletion FISH study should be considered in patients with cardiac lesions particularly conotruncal abnormality with or without syndromic problems [craniofacial dysmorphism and developmental delay] to provide an appropriate genetic counseling with more accurate estimation of recurrence risk and ultimately prenatal diagnosis in affected families

Comparison of neural network and principal component-regression analysis to predict the solid waste generation in Tehran

Municipal solid waste [MSW] is the natural result of human activities. MSW generation modeling is of prime importance in designing and programming municipal solid waste management system. This study tests the short-term prediction of waste generation by artificial neural network [ANN] and principal component-regression analysis. Two forecasting techniques are presented in this paper for prediction of waste generation [WG]. One of them, multivariate linear regression [MLR], is based on principal component analysis [PCA]. The other technique is ANN model. For ANN, a feed-forward multi-layer perceptron was considered the best choice for this study. However, in this research after removing the problem of multicolinearity of independent variables by PCA, an appropriate model [PCA-MLR] was developed for predicting WG. Correlation coefficient [R] and average absolute relative error [AARE] in ANN model obtained as equal to 0.837 and 4.4% respectively. In comparison whit PCA-MLR model [R= 0.445, MARE= 6.6%], ANN model has a better results. However, threshold statistic error is done for the both models in the testing stage that the maximum absolute relative error [ARE] for 50% of prediction is 3.7% in ANN model but it is 6.2% for PCA-MLR model. Also we can say that the maximum ARE for 90% of prediction in testing step of ANN model is about 8.6% but it is 10.5% for PCA-MLR model. The ANN model has better results in comparison with the PCA-MLR model therefore this model is selected for prediction of WG in Tehran

Molecular basis of G6PD deficiency: Current status and its perspective

Glucose-6-phosphate dehydrogenase is an essential enzyme to cell growth. Its deficiency of enzyme plays an important role in senescence and death signaling. Also, it is actually the most common clinically important enzyme defect, not only in hematology, but also among all human known diseases. Clinical consequences of enzyme deficiency are: neonatal hyperbilirubinemia, acute hemolytic anemia, and chronic hemolytic anemia. The enzyme gene spans 18 kb on the X chromosome [xq28] and contains 13 exons. Its promoter is embedded in a CpG island that is conserved from mice to humans. The development of a number of PCR-based methods for the detection of known mutations in Glucose- 6-phosphate dehydrogenase has made it possible to detect enzyme deficiency and identify the specific mutation responsible with relative ease. We will discuss the mentioned clinical manifestations of glucose-6-phosphate dehydrogenase deficiency, Genetics, biochemistry and pathophysiology of the enzyme in details using newer published data and present most of the studies in Iranian population

Relation between Helicobacter pylori and nausea and vomiting in pregnant women

Gestational nausea and vomiting in pregnant women have a high prevalence. The disorder will usually be better after the third trimester but, in some cases, it persists throughout pregnancy and makes the life of pregnant women disturbed. This case-control retrospective study was conducted to determine the relation between Helicobacter pylori and nausea as well as vomiting in pregnant women referring to the healthcare centers affiliated to Mashhad University of Medica Sciences in 2006. 187 pregnant women at the third trimester of their pregnancy were selected. According to the experience of nausea and vomiting from the first trimester, they were divided into two groups: 89 women with the disorder and 98 women without it. A questionnaire in three parts was used for data collection: demographic information, history of nausea and vomiting, and socioeconomic status. The questionnaire was validated by context validity and reliability by test-retes method. Anti-Hp immunolobin G [IgG] serum antibody wastested by ELISA it determine seropositivity [r=0/89]. The result showed a significant relation between helicobacter pylori and nausea and vomiting during pregnancy. The subjects did not have significant differences in terms of height, job, education of spouse, husbands' job, pregnancy and BMI except for age and socioeconomic status [P=0.037 and P<0.001 respectively]. The results may show that nausea and vomiting during pregnancy can be prevented by diagnosing helicobacter pylori infection in women. Also, it seems that there should be a training program in knowing Helicobacter pylori infection and its complications. Considering the results of this research, studying women with nausea and vomiting during pregnancy for helicobacter pylori infection is advisable

Two case reports of Kikuchi-Fujimoto disease

Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is a rare but important etiology of cervical lymphadenopathy in young women. This disease is self limited and improves during 2-8 months. Diagnostic key is the pathology of involved lymphnode. Association of the disease with viral and autoimmune disease is not proved yet. In this article two cases of Kikuchi-Fujimoto disease are reported. The first case was a 31 years old female patient with sever fever and right axillary lymphodenpathy [size: 5x7cm] in which one month after the disease, diagnosis was proved by pathology studies. This patient has erythematous patches in her face and nose in several times that were improved spontaneously. The second case was a 20 years old female patient with fever, chiH, headache, weigh loss and cervical lymphadenopathy [size: 2x1 cm]. She received antibiotic at several times without any improvement. Finally after 5 months since the beginning of symptoms, the disease was diagnosed as Kikuchi-Fujimoto disease by surgical excision of lymhnode and pathology studies. After the surgery two small lymphnodes were appeared around the surgical site. In differential diagnosis of lymphadenpathy especially cervical in young women, Kikuchi-Fujimoto should be considered. Consumption of antibiotic in lymphadenopathy without clear diagnosis should be avoided. After diagnosis of Kikuchi-Fujimoto, long term work up for recurrence or the appearance of autoimmune disease symptoms is necessary

[ relationship between Helicobacter pylori infection and anemia in pregnant women]

Iron deficiency anemia has a high prevalence in women of reproductive age, especially in pregnant women [50%], with serious consequences on the mother and the fetus. Anemia is responsible for about 10-15% of all maternal deaths worldwide. There are different and sometimes contradicting reports on the role of Helicobacter pylori in causing anemia. On the other hand, Helicobacter pylori infection and its well-known complications are of high prevalence in developing countries. Therefore, the present study was conducted to determine the relationship between Helicobacter pylori and anemia. This study was retrospectively conducted on 187 pregnant women who were at their third trimester and attended the Health Centers affiliated with Mashad University of Medical Sciences for prenatal care during 2006. Based on hemoglobin assessment done in the first trimester and kept in their health records, the participants were divided into two groups: anemic [94 women] and healthy [93 women] groups. Demographic information and nutrition questionnaires were completed. Tests for hemoglobin, ferritin, and Helicobacter pylori infection, using Elisa method for the detection of IgA and IgG, and antibody titration were conducted. The data from this study were analyzed by SPSS software, version 13, using descriptive [Mean, standard deviation and odds ratio] and inferential statistics [Independent t-test, chi-squared, Mann-Whitney test, analysis of variance and logistic regression]. P-values less than 0.05 were considered significant. The subjects in the two groups did not have significant differences in terms of age, job, education, husband and #101;s education, husband and #101;s job, number of pregnancies and economic status. The rate of Helicobacter pylori infection showed a significant difference between the two anemic and non-anemic groups [p=0.01]. It was also shown that hemoglobin concentration and ferritin, during the third trimester of pregnancy in Helicobacter pylori infected cases were lower compared to that of the healthy ones [p<0.001]. On the other hand, the changes of hemoglobin during the first and the third trimesters of pregnancy in the two groups showed a significant difference [p<0.001]. The amount of hemoglobin during the third trimester of pregnancy in the Helicobacter pylori infected group had no significant increases in comparison to theirs at the first trimester, despite iron supplementation. It seems that there is a relationship between Helicobacter pylori infection and anemia in pregnant women, therefore it is suggested that tests for Helicobacter pylori infection be included in preconceptional consultations, especially for women who have a history of anemia or persistent anemia, as this will be both wise and economic

role of stress, sociotropy and autonomy in depression

Beck [1983] claimed that personality style of sociotropy and autonomy in a vulnerable factor depression that interacts with stress congruent with same personality style. This study investigates the role of stress, sociotropy and autonomy in depression in a retrospective and case control design. 156 major depressed patients were compared with 78 never depressed and normal people based on sex, age, life, events, sociotropy and autonomy, congruent stresses. Results showed that depressed patients experienced significantly more stresses than normals. Also, sociotrop and autonomous patients had experienced significantly different stresses that were congruent with their personality style. Results supported the role of stress in depression and congruency hypothesis that Beck asserted

Down's syndrome: cytogenetic studies in 150 case in Tehran

Cytogenetic studies were performed on 150 cases of Down's syndrome [DS] in lran. The standard trisomy 21 was found in 132 [88%] and translocation-trisomy 21 [+21] in 18 [12%] patients, i.e., t [21,21] in 1[0.63%] and mosaicism in 17[11.33%] cases. The comparison of the frequencies for mosaicism between different populations such as Denmark, Hungary, Egypt, Iraq, India, Australia and Iran demonstrated a difference in geographic distribution. There was a high incidence in the north of Europe towards Egypt and Iraq which decreased towards Iran and further towards the eastern region in the Indian ocean and India and further decreased towards Australia. Statistical analyses demonstrated significant differences between the data in Iran and Copenhagen, Hungary and Australia for mosaicism and translocation +21, and India, for translocation +21. The occurrence of translocation +21 decreased significantly from Denmark towards Egypt in Africa and Iraq in southwest Asia, then it increased from Iran towards Australia in the Pacific ocean.The comparison of cells having satellite associations [SA], significantly indicated the involvement of two and three SAs in DS cases. The study on the position of chromosomes in the metaphase plate, the occurrence of chromatid breaks and endoreduplication did not present any significance in DS cases

Molecular studies on the distribution of beta-thalassemia in Iran: the basis for prenatal diagnosis

By application of modern recombinant DNA technology, especially the polymerase chain reaction [PCR]/dot-blot hybridization techniques, we have investigated the molecular basis of Beta -thalassemia from four different regions of Iran: central, south-east, south and north. In this study, the DNA samples were isolated from patients and for the identification of the mutations, the 6 oligonucleotide probes for the mutations of IVS.l/nt. 110, IVS.l / nt.6, IVS. L / nt. l, nonsense codon 39, frameshift codon 8 and IVS.2/nt.l were selected with respect to their relative frequency in the neighbouring country, Turkey. Four mutations accounted for 76.2% and of these, the most frequent was the nonsense codon 39 mutation, which accounts for 60.3% of the Beta -thalassemia alleles tested. The remainder, in decreasing order of frequency,were frame shift cod on 8[9.5%],IVS.l/nt.6[4.8%]and IVS.l/nt.l 10[1.6%]. No hybridization was observed with the probes corresponding to the mutations of IVS.l/nt.l[G/A] and IVS.2/nt.l[G/A].These results also revealed that the distributions of different types of mutations were different in the four regions. This information and the introduction to the methodology used in this study will facilitate the prenatal diagnosis of the disease in Iran