CFTR mutation analysis in Western Iran: identification of two novel mutations

Background: Cystic fibrosis [CF] is one of the most common autosomal recessive disorders in Caucasian population. The incidence of disorder varies among different religious, ethnic and geographical isolates. The aim of this study was to identify the spectrum and the frequency of known and unknown disease-causing mutations in Iranian CF patients

Methods: Genomic DNA was extracted from peripheral whole blood with a QI-Aamp DNA Mini-Kit. Mutation analysis was done in the CFTR gene including complete coding region and intron/exon boundaries using a direct sequencing method

Results: In general, ten mutations were identified in 27 CF cases. Two out of 10 mutations, 754delT and GGTGGCdel/TTGins, were reported as novel mutations. The most common observed mutations in patients were R334W [40.74%], DeltaF508 [18.5%], K710X [12.96%] and D110H [5.5%], 1897C>G [1.85%], R1162X [1.85%], S466X [1.85%] and T1036I [1.85%]

Conclusion: The finding indicated a unique mutation panel which can be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran. Although DeltaF508 is the most common mutation in other populations including Caucasian, this mutation seem not to have an important role in Iranian CF patients. Findings suggest that a different approach in molecular genetics diagnostic strategies in Middle Eastern countries including Iran should be considered

Mutation analysis of exons 10 and 17a of CFTR gene in patients with cystic fibrosis in kermanshah province, Western Iran

Cystic fibrosis [CF] is the most common genetic disorder with autosomal recessive inheritance among Caucasian populations. So far, more than 1950 different mutations were identified in cystic fibrosis transmembrane conductance regulator [CFTR] gene. CFTR gene has 27 exons. The type and distribution of mutations vary widely among different countries and/or ethnic groups. Therefore, a comprehensive analysis was performed on exon10 and exon17a of CFTR gene in CF patients in the Kermanshah province, western Iran. We tested 27 patients admitted to the medical genetics laboratory of Kermanshah University of Medical Sciences. The patients were from different cities of Kermanshah province. All the patients had the clinical signals and two positive sweat tests. After filling agreement forms and questionnaire, the peripheral blood sampling and DNA extraction were done. DNA samples were extracted. PCR and sequencing special PCR were done. Finally analysis of the results with DNA sequencing analysis version 5.2 software was performed. CFTR mutations analysis identified 4 different mutations in our CF patients. The disease-causing mutations were p.F508del [delta F508] [14.81%], p.S466X [1.85%], and p.T1036I [1.85%]. M470V polymorphism with frequency of 74.1% was found in 23 patients [17 homozygous and 6 heterozygous]. Three disease-causing mutations in CF patients in the present study account for approximately 18.51% of mutations. The frequency of p.F508del, the most common mutation was 16-18.1% in Iranian population. The results of the present study can be applied for genetic counseling, population screening and prenatal diagnosis

Gene and environment interaction in familial suicidal behavior: a single family with 4 committed suicides

Family history of suicide is among the strongest predictors of suicide risk. From the context of gene by environment interactions, this manuscript presents a case study of the "M" family, which experienced 4 committed suicides within a short time period. Over the course of 5 years, the father and 3 sons committed suicide. Suicidal ideations developed in several other members of the family. The family's suicide risk appears to have stemmed from both environmental and genetic factors, and likely from an interactive effect between both. Environmental factors included low level of education, opium dependency among male family members, unemployment, and poverty, and limited access to mental health services. Genotype analyses of A218C polymorphism among surviving family members revealed that all individuals were associated with the gene variation [genotypes CC and AC] in tryptophan hydroxylase. The genetic by environmental interaction influence is discussed

[Molecular analysis of alpha globin gene deletions among patients with microcytic hypochromic anemia in Kermanshah-Iran]

The majority of alpha-thalassemi mutations are deletions of one or both alpha- globin genes. Since the Iranian populaion is a mixture of different ethnic groups, frequency and distribution of globin mutations in various regions of the country need to be clarified. The aim of this study was to determine the common alpha globin gene deletions among individuals with hypochromic microcytic anemia in Kermanshah province. Following the initial evaluation, 92 patients [47 women and 45 men] were found as microcytic hypochromic [MCV < 80 fl and MCH< 27 pg] anemia and selected for this study. All samples were analyzed for detection of four alpha-gene deletions [-alpha3.7,-alpha4.2,- [alpha] 20.5 and --MED] by GAP-PCR technique. After amplification, 10microl of PCR product was electrophoresed through 1.2% agarose gel and bands were visualized by staining gel in ethidium bromide solution and photographed under a UV transilluminater. 45 patients had -alpha 3.7 single gene deletion. In patients with -alpha3.7 deletion, in both homozygous and heterozygous states, MCH was lower than normal ranges. However, the percent of HbA2 was in normal range. In this study, other common deletional mutations, including - [alpha]20.5, -alpha4.2 and --MED were not found. The results of persent study showed that the frequency of -alpha3.7 single gene deletion among patients with microcytic hypochromic anemia in Kermanshah province was 48.9%

Mutation analysis of CFTR gene in 70 Iranian cystic fibrosis patients

Cystic fibrosis [CF] is the most common inherited disorder in Caucasian populations, with over 1400 cystic fibrosis transmembrane conductance regulator [CFTR] mutations. The type of mutations and their distributions varies widely between different countries and/or ethnic groups. Seventy Iranian cystic fibrosis patients were screened for the CFTR gene mutation using ARMS/PCR [amplification refractory mutation system] for the following mutations: delta F508, N1303K, G542X, 1717-1G>A, R553X, W1282X, G551D, 621+1G>T, delta I 507 and R560T. Single strand conformation polymorphism [SSCP] analysis of exons 3, 7, 10, 11 and 17b, including both the exon/intron junctions, of the CFTR gene was performed in patients in whom no mutation could be identified on one or both CFTR genes. As a result of this screening, only three mutations were found: delta F508 mutation was found in 25 [17.8%] alleles, N1303K in six [4.3%] alleles and G542X in five [3.6%] alleles. Thus, a total of 3 mutations cover 25.7% of CF alleles. These finding will be used for planning future screening and appropriate genetic counseling programs in Iranian CF patients