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1.
Med J Islam Repub Iran ; 33: 88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696082

RESUMO

Background: The analysis of haplotypes/mini-haplotypes in the PAH gene has been used as an informative tool in several genetic anthropology studies. Considering the notion that Iranian population is one of the most heterogeneous i the world, this study was conducted to evaluate the association of VNTR-STR mini-haplotypes with the PAH gene mutations in PKU patients in Kermanshah province. Methods: A total of 24 unrelated Kurdish PKU patients with the known PAH gene causing mutations and 72 healthy controls were selected. The DNA fragments containing VNTR and STR systems were amplified by polymerase chain reaction (PCR). For VNTR system, PCR products were separated using electrophoresis on 2.5% agarose gel. For STR system, the samples were analyzed using DNA sequencing analysis version 5.2 software. Results: Overall, 5 PAH-VNTR-alleles, including VNTR3, 7, 8, 9, 12, and 3 PAH-STR-alleles, including STR238, 242, and 250, were detected in this study. VNTR3 and 8 alleles had the most frequency among healthy controls. Also, 6 different mini-haplotype alleles were found to be associated with PKU chromosomes. The 2 most prevalent mutations in Kermanshah province, IVS2+5G>C and IVS9+5G>A, were strongly linked to mini-haplotypes 9/242 and 8/238, respectively. Conclusion: The distributions and frequencies of VNTR alleles in Kurdish population have the most similarity to alleles previously described in European Caucasian families. Moreover, since the most common mutations in Kermanshah PKU chromosomes are rare and this was the first study on mini-haplotypes VNTR/STR among Iranian Kurdish PKU patients, given that this study was the first of its kind, it was not possible to compare its results with that of other studies on Iranian and non-Iranian populations.

2.
Hemoglobin ; 43(2): 107-111, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31304855

RESUMO

α-Thalassemia (α-thal) is one of the most common genetic disorders worldwide. The aim of this study was to investigate for the first time the α-thal mutation spectrum in the Lak population living in Lorestan Province, Iran. One hundred and seventy-six α-thal carriers participated in the study. Multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing were used for the detection of different mutations on the α-globin (HBA1 and HBA2) genes. A total of 11 different mutations was identified. The -α3.7 (rightward; NG_000006.1: g.34164_37967del3804) deletion was observed most frequently (56.35%), followed by α-5 ntα (HBA2: c.95+2_95+6delTGAGG), αpolyA2α (HBA2: c.*92A>G) and - -MED I (NG_000006.1: g.24664_41064del16401), with frequencies of 15.47, 9.39, and 6.08%, respectively. These four mutations accounted for more than 87.0% of the total mutated alleles. Moreover, 19 different genotypes were identified. The types and distribution pattern of the mutations identified in this study, in comparison with other studies conducted in Iran, was most similar to the Kurdish population of Kermanshah Province, Iran. Due to the lack of information on α-thal in Lorestan Province, it was not possible to compare the mutation spectrum in the Lur and Lak populations. In conclusion, our results may help in setting up a strategy for an α-thal screening program and genetic counseling in the Lak people.


Assuntos
Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Genótipo , Heterozigoto , Humanos , Irã (Geográfico)/epidemiologia , Irã (Geográfico)/etnologia , Análise de Sequência de DNA/métodos , Talassemia alfa/etnologia
3.
Hemoglobin ; 43(1): 23-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31146650

RESUMO

ß-Thalassemia (ß-thal) is the most frequently observed hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Detecting thalassemia mutations are necessary for prenatal diagnosis (PND) programs leading a better quality of life for the patients, as well as a reduction in the cost of their medical care. There are more than 900 different genomic mutations of the ß-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we identified a mid-intronic mutation at IVS-II-821 (A>C) (HBB: c.316-30A>C) position in the HBB gene of an Iranian proband and two of her siblings that was associated with ß-thal clinical features. Direct DNA sequence analysis was performed by mutation scanning of the ß-globin gene. Based on the observed ß-thal phenotype and bioinformatics analysis results, we concluded that this ß-globin gene mutation was associated with a mild phenotype of ß-thal through activating potential splice sites by creating exonic splicing enhancers (ESEs), exon-identity element (EIE) and exonic splicing regulatory sequences (ESRs) sites.


Assuntos
Éxons , Íntrons , Mutação , Fenótipo , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Adolescente , Adulto , Alelos , Índices de Eritrócitos , Feminino , Frequência do Gene , Humanos , Irã (Geográfico) , Masculino , Adulto Jovem , Talassemia beta/sangue
4.
Hemoglobin ; 43(1): 18-22, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31096791

RESUMO

ß-Thalassemia (ß-thal) is one of the most common hemoglobinopathies worldwide and is caused by mutations on the ß-globin (HBB) gene. The aim of the present study was to determine the mutation spectrum of the ß-globin gene in ß-thal carriers who were originally from Hamadan Province, Western Iran. Two hundred and eighty-two ß-thal carriers participated in the study. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and direct sequencing were used for detection of different mutations. A total of 25 different mutations, including 21 ß-thal mutations and four other hemoglobin (Hb) variants, in 280 ß-thal carriers (99.3%) were detected in the present study. Three types of mutations including IVS-II-1 (G>A) (HBB: c.315+1G>A) (26.24%), codons 8/9 (+G) (HBB: c.27_28insG) (14.54%) and codons 36/37 (-T) (HBB: c.112delT) (12.76%) accounted for more than 50.0% of the identified mutations. Moreover, IVS-I-110 (G>A) (HBB: c.93-21G>A), codon 44 (-C) (HBB: c.135delC) and IVS-I (25 bp deletion) (HBB: c.93-21_del), had frequencies of 7.09, 7.09 and 5.67%, respectively. Allele frequencies of the remaining 19 mutations were less than 5.0%. This study is the first comprehensive study on a large sample size in Hamadan Province, Iran. In conclusion, the present study significantly increased the spectrum of HBB gene mutations in Hamadan Province compared with previous studies. Therefore, these results can be helpful in identifying ß-thal carriers and at-risk fetuses through prenatal diagnosis (PND).


Assuntos
Mutação , Globinas beta/genética , Talassemia beta/genética , Alelos , Códon , Índices de Eritrócitos , Feminino , Frequência do Gene , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Vigilância da População , Prevalência , Talassemia beta/sangue , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
5.
Mol Biol Rep ; 46(1): 741-749, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30506510

RESUMO

Rheumatoid arthritis (RA) is considered as a long-term autoimmune disorder. Gene polymorphism and oxidative stress might be involved in the pathogenesis of the disease. We aimed to determine the association between PON-1L55M polymorphism and its effects on inflammatory markers such as anti-cytroline circulated-peptide (CCP)-antibodies, C-reactive protein (CRP), neopterin serum concentration, arylesterase (ARE) and butyrylcholinesterase (BuChE) activities and total-antioxidant-capacity (TAC) level with the activity of disease in RA patients. This case-control study consisted of 419 RA patients and 397 gender-age-matched unrelated healthy controls from the west of Iran. PON1-L55M polymorphism was detected by real-time-PCR. The TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. The PON1-M55 allele was associated with increased risk of the RA in cases with moderate or high activity (OR = 1.43, p = 0.023) and also in cases with the presence of anti-CCP antibody (OR = 1.51, p = 0.009). Synergistic effects of PON1 M55 and Q192 alleles resulted in 2.14 times (p = 0.021) increased disease activity among RA patients with moderate or high activity of the disease. RA patients carried both M (PON1 L55M) and Q alleles (PON1Q192R) had higher concentrations of neopterin (p = 0.003), anti-CCP-antibody (p < 0.001) and CRP (p = 0.026) and significantly lower TAC level (p < 0.001) and ARE (p < 0.001) activity compared to controls. The current study suggests there might be a relationship between genetic and activity of PON. Also, the PON1L55M and PON1Q192R could act in synergy to increase the risk of RA and enhance the level of oxidative stress markers.


Assuntos
Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Arildialquilfosfatase/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Alelos , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/patologia , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
6.
J Reprod Infertil ; 19(1): 3-9, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850441

RESUMO

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 QIAamp 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%), ΔF508 (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 ΔF508 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.

7.
Iran J Med Sci ; 43(3): 318-323, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29892150

RESUMO

Phenylketonuria (PKU) is one of the most common known inherited metabolic diseases. The present study aimed to investigate the status of molecular defects in phenylalanine hydroxylase (PAH) gene in western Iranian PKU patients (predominantly from Kermanshah, Hamadan, and Lorestan provinces) during 2014-2016. Additionally, the results were compared with similar studies in Iran. Nucleotide sequence analysis of all 13 exons and their flanking intronic regions of the PAH gene was performed in 18 western Iranian PKU patients. Moreover, a variable number of tandem repeat (VNTR) located in the PAH gene was studied. The results revealed a mutational spectrum encompassing 11 distinct mutations distributed along the PAH gene sequence on 34 of the 36 mutant alleles (diagnostic efficiency of 94.4%). Also, four PAH VNTR alleles (with repeats of 3, 7, 8 and 9) were detected. The three most frequent mutations were IVS9+5G>A, IVS7-5T>C, and p.P281L with the frequency of 27.8%, 11%, and 11%, respectively. The results showed that there is not only a consanguineous relation, but also a difference in PAH characters of mutations between Kermanshah and the other two parts of western Iran (Hamadan and Lorestan). Also, it seems that the spectrum of mutations in western Iran is relatively distinct from other parts of the country, suggesting that this region might be a special PAH gene distribution region. Moreover, our findings can be useful in the identification of genotype to phenotype relationship in patients, and provide future abilities for confirmatory diagnostic testing, prognosis, and predict the severity of PKU patients.

8.
Int J Hematol Oncol Stem Cell Res ; 11(3): 225-230, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28989589

RESUMO

Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Various genetic and epigenetic factors have been found to be influential in such patients. Methylation silencing of APAF-1, a putative tumor suppressor gene (TSG), has been found in several human malignancies. In this study, we explored the association of APAF-1 methylation status with AML patients. Materials and Methods: We studied the methylation status of APAF-1 gene in 101 AML patients and 50 healthy subjects as controls. Genomic DNA was extracted from leukocytes in peripheral blood or bone marrow and the methylation status of APAF-1 gene promoter was detectedusing methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. Gene expression was analyzed using real time RT-PCR. Results: The prevalence of methylated (MM) and hemi-methylated (MU) CpG dinucleotides within the APAF-1 gene promoter of AML patients was 12 (11.9%) and 45 (44.6%), respectively, while no methylation was detected in the control samples (p < 0.001). Our results showed a higher frequency of methylated APAF1 in FLT3-ITD mutated cases (p=0.04). APAF1 mRNA expression was significantly lower in methylated cases compared with normal cases. Conclusion: The present study indicated the increased frequency of hypermethylation of APAF-1 gene promoter in AML patients. APAF-1 aberrant CpG island methylation was associated with transcriptional downregulation in AML patients. Therefore, promoter methylation of APAF-1 gene could be considered as an epigenetic factor that contributes to the development of AML.

9.
Hemoglobin ; 41(1): 44-46, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28475449

RESUMO

Thalassemia is the most common inherited disorder in Iran. There are approximately 800 different genomic alterations of the ß-globin gene described in the HbVar database. In this study, we identified a novel mutation in a 21-year-old woman [IVS-II-648/649 (-T); HBB: c.316-202del)] and describe its clinical implications. Two other members of this family, all with hematological and clinical features associated with ß-thalassemia (ß-thal), also carried this mutation. The molecular diagnosis of the ß-globin gene mutation was performed by direct sequencing. Based on the observed ß-thal phenotype and in silico analysis results, we concluded that this novel ß-globin gene mutation was associated with the mild phenotype of ß-thal.


Assuntos
Íntrons , Fenótipo , Deleção de Sequência , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Adulto , Alelos , Pré-Escolar , Análise Mutacional de DNA , Índices de Eritrócitos , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Talassemia beta/sangue
10.
Oncol Lett ; 13(5): 3277-3284, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28521434

RESUMO

Aberrant promoter methylation of genes is a common epigenetic alteration in colorectal cancer (CRC). In the present study, spastic paraplegia 20 (SPG20) promoter-methylated DNA, as a potential diagnostic biomarker, was investigated in plasma and tumor tissue samples from patients with CRC. To the best of our knowledge, the quantification of SPG20 promoter-methylated DNA in plasma samples remains unreported. SPG20 promoter methylation was investigated in 32 paired tumor and healthy adjacent tissues, 37 plasma samples from patients with CRC, and in 37 plasma samples from a healthy control group, using the MethyLight method. The percentage of methylated reference (PMR) values was determined for each sample, and the sensitivity and specificity of this unique biomarker were evaluated. PMR values were significantly higher in plasma samples from patients with CRC compared with in those from the control group (P<0.05). Plasma specimens from patients and healthy controls exhibited median PMR values of 7.7 (95% CI, 4.15-15.28) and 0.59 (95% CI, 0.14-1.12), respectively. Notably, the median PMR values were identified as 42.39 (95% CI, 27.69-72.26) and 3.61 (95% CI, 1.07-5.29) in tumor and adjacent healthy tissues, respectively. Using receiver-operating characteristics curve analysis, the area under curve (AUC) was demonstrated to be 0.984 for plasma samples, exhibiting a sensitivity of 81.1% and a specificity of 96.9%. Furthermore, the AUC was 0.996 for tissue samples, revealing a sensitivity of 93.8% and specificity of 99.96%. Results from the present study indicate that the identification of SPG20 promoter-methylated DNA in plasma is a potential diagnostic biomarker for the detection of CRC. Furthermore, the results demonstrate a satisfactory sensitivity and specificity, indicating the importance of SPG20 methylation as a novel noninvasive biomarker.

11.
Hemoglobin ; 39(6): 403-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26287614

RESUMO

Thalassemia is a hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Although thalassemia mostly affects developing countries, there is limited knowledge of its accurate frequency and distribution in these regions. Knowing the prevalence of thalassemia and the frequency of responsible mutations is therefore an important step in the prevention and control program as well as treatment strategies. α-Thalassemia (α-thal) is prevalent in Middle East Asian populations, including Iran. In this study, 678 unrelated α-thal carriers, attending the Kermanshah Medical Genetics Laboratory, Kermanshah, Iran, were investigated for α-globin gene mutations by multiplex polymerase chain reaction (PCR) and direct sequencing. The most common mutation among our patients was -α(3.7) (rightward) (60.9%) deletion, which is also known to occur in high frequencies in other parts of Iran, in Southeast Asia and Mediterranean countries. Other prevalent α-thal mutations were α(-5 nt) (10.6%), α(polyA4) (9.9%), α(polyA6) (3.7%), - -(MED) (3.2%), -α(4.2) (leftward) (3.1%) deletion and codon 59 (Hb Adana; HBA1: c.179 G > A) (2.5%). These comprehensive new data are useful for establishing a screening strategy for the effective control of α-thal in Kermanshah Province.


Assuntos
Mutação , alfa-Globinas/genética , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Análise Mutacional de DNA , Índices de Eritrócitos , Feminino , Genótipo , Heterozigoto , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Fenótipo , Talassemia alfa/sangue
12.
J Reprod Infertil ; 15(1): 49-56, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24696795

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: CFTR mutations analysis identified 4 different mutations in our CF patients. The disease-causing mutations were p.F508del (ΔF508) (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). CONCLUSION: 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.

13.
Metab Brain Dis ; 29(1): 131-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24048906

RESUMO

Phenylketonuria (PKU) is an autosomal recessive disorder characterized by a mutation in the phenylalanine hydroxylase (PAH) gene. Untreated PKU can lead to mental retardation, seizures, and other serious medical problems. This study was designed to investigate the status of molecular defects in the PAH gene and their association with polymorphisms in Kurdish patients with PKU in the Kermanshah province, western Iran. The study was conducted on 27 unrelated patients with PKU over a 2-year period (from 2010 to 2012). All 13 exons plus exon-intron boundaries of the PAH gene were analyzed and we identified 15 different mutations, including two novel mutations, in 51 of the 54 mutant alleles (diagnostic efficiency of 94.4 %). IVS4 + 1G > C (c.441 + 1G > C) and IVS7 - 5 T > C (c.843 - 5 T > C) are novel mutations that have not been reported in the academic literature or the PAH locus database ( http://www.pahdb.mcgill.ca ); therefore, they may be specific to the Kurdish population. IVS2 + 5G > C and IVS9 + 5G > A were the two most prevalent mutations in our sample, with frequencies of 26 % and 17 %, respectively. The second most common mutations were p.R261X, IVS10 - 11G > A, p.K363 > Nfs and IVS7 - 5 T > C, with each showing a relative frequency of 7.4 %. All other detected mutations, including p.F55 > Lfs, p.R176X, p.R243Q, p.V230I, p.R243X, p.R261Q, IVS8 - 7A > G and p.E390G had frequencies of less than 4 %. The present study showed that there is a distinct difference in the characteristics of PAH mutations between the Kermanshah province and other parts of Iran, suggesting that Kermanshah may have a unique population distribution of PAH gene mutations. Iran lies on the route of major ancient movements of the Caucasian people toward the Mediterranean basin, and Kermanshah has previously been called the gateway to Asia. Most of the mutations identified in this study are common in the Mediterranean region. Therefore, our findings are consistent with the historical and geographical links between the Iranian population and the populations of Mediterranean region.


Assuntos
Grupos Étnicos/genética , Mutação , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Polimorfismo Genético , Adolescente , Alelos , Criança , Pré-Escolar , Códon sem Sentido , Consanguinidade , Análise Mutacional de DNA , Grupo com Ancestrais do Continente Europeu/genética , Éxons/genética , Feminino , Frequência do Gene , Migração Humana , Humanos , Íntrons/genética , Irã (Geográfico)/epidemiologia , Masculino , Região do Mediterrâneo , Mutação de Sentido Incorreto , Fenilcetonúrias/etnologia , Análise de Sequência de DNA , Deleção de Sequência , Adulto Jovem
14.
Hemoglobin ; 37(6): 544-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23915319

RESUMO

ß-Thalassemia (ß-thal) is a hereditary autosomal disorder with decreased or absent ß-globin chain synthesis. Two hundred and one unrelated ß-thal carriers, attending the Kermanshah Medical Genetics Laboratory, Kermanshah, Iran, were investigated for ß-globin gene mutations by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and direct sequencing. Eighteen different mutations were identified in these subjects. Four of the mutations accounted for about 75.0% of the studied cases. IVS-II-1 (G>A) was the most frequent (45.8%) followed by codons 8/9 (+G) (15.9%), IVS-I-110 (G>A) (8.0%), IVS-I-6 (T>C) (5.5%), IVS-I-1 (G>A) (3.5%) and codon 44 (-C) (3.5%); the remaining 12 mutations were present with a frequency less than 3.0%. The mean corpuscular volume (MCV) values for males and females were 63.7 ± 3.7 and 63.2 ± 3.2 fL, respectively, while these values were 19.3 ± 1.6 and 19.3 ± 1.4 pg for mean corpuscular hemoglobin (Hb) (MCH). The mean Hb A2 values for males and females were 4.4 ± 0.5 and 4.1 ± 0.6%, respectively. This study provides a distribution guide for ß-thal mutations in Kermanshah Province, West Iran.


Assuntos
Mutação , Globinas beta/genética , Talassemia beta/sangue , Talassemia beta/genética , Índices de Eritrócitos , Geografia , Humanos , Irã (Geográfico) , Fenótipo
15.
Indian J Hum Genet ; 19(4): 454-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24497712

RESUMO

BACKGROUND: Defects either in phenylalanine hydroxylase (PheOH) or in the production and recycling of its cofactor (tetrahydrobiopterin [BH4]) are the causes of primary hyperphenylalaninemia (HPA). The aim of our study was to investigate the current status of different variants of HPA Kurdish patients in Kermanshah province, Iran. MATERIALS AND METHODS: From 33 cases enrolled in our study, 32 were identified as HPA patients. Reassessing of pre-treatment phenylalanine concentrations and the analysis of urinary pterins was done by high-performance liquid chromatography method. RESULTS: A total of 30 patients showed PAH deficiency and two patients were diagnosed with BH4 deficiency (BH4/HPA ratio = 6.25%). Both of these two BH4-deficient patients were assigned to severe variant of dihydropteridine reductase (DHPR) deficiency. More than 75% of patients with PAH deficiency classified as classic phenylketonuria (PKU) according their levels of pre-treatment phenylalanine concentrations. CONCLUSION: Based on the performed study, we think that the frequency of milder forms of PKU is higher than those was estimated before and/or our findings here. Furthermore, the frequency of DHPR deficiency seems to be relatively high in our province. Since the clinical symptoms of DHPR deficiency are confusingly similar to that of classic PKU and its prognosis are much worse than classical PKU and cannot be solely treated with the PKU regime, our pilot study support that it is crucial to set up screening for BH4 deficiency, along with PAH deficiency, among all HPA patients diagnosed with HPA.

16.
Indian J Hum Genet ; 18(3): 290-3, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23716935

RESUMO

BACKGROUND: Phenylketonuria (PKU) is an inborn error of amino acid metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). According to PAH database, exons 6 and 7 and their flanking introns of PAH gene contain the greatest number of mutant alleles. Therefore, as a preliminary study, nucleotide sequence analysis of exons 6 and 7 of the PAH gene has been performed in 25 PKU patients whose ancestors lived in Kermanshah province of Iran. To date, there has been no mutation data describing the genotypes of the PKU disease in this Kurdish ethnic region background. MATERIALS AND METHODS: Twenty-five patients (aged between 2 and 23 years) participated in this study. The DNA fragments containing two exons of the PAH gene [6 and 7] and their exon-flanking intronic sequences were amplified and sequenced. RESULTS: The total of detected mutations were R261X (8%), R176X (4%), R243Q (4%), R243X (2%) and R261Q (2%), as they accounted for 20% of all mutant alleles in this study. The identified polymorphisms are: IVS5 -54 G > A (22%), Q232Q (8%) and V245V (4%). All of the detected mutations in this study are related to CpG dinucleotides in the PAH gene sequence. CONCLUSION: The frequency of R261X, the most common mutation in our study, in Iranian population is <5%. Furthermore, there is no report of detection of R176X and R243Q in Isfahan and Azeri Turkish populations. These findings confirm the common Mediterranean mutations in this local population, although with more or lower frequencies than those reported in other related studies in Iran. Therefore, it may be necessary to study the PAH gene mutations in other provinces of Iran separately.

17.
Saudi Med J ; 32(10): 1073-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22008930

RESUMO

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.


Assuntos
Família , Predisposição Genética para Doença , Suicídio , Adolescente , Adulto , Feminino , Humanos , Masculino
18.
Mol Biol Rep ; 38(8): 5421-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21465165

RESUMO

The role of the paraoxonase (PON1) codon 192 polymorphism [glutamine (Q)/arginine (R)] in coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate whether the PON1 gene polymorphism is an independent risk factor for severity of coronary artery disease in patients from west of Iran. The PON1-Arg-192 genotypes were detected by PCR-RFLP in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control without CAD or diabetes. The frequency of PON1-Arg-192 allele was significantly higher in the CAD (23.4 vs. 16%, P = 0.032) than in the control group and there was a higher risk of developing CAD (OR = 1.6, P = 0.02). In addition, this difference remained significant after adjustment for without history of diabetes (OR = 1.47, P = 0.048), presence of normolipidemia and absence of history of blood pressure (OR = 1.4, P = 0.05). This result indicated PON1-Arg-192 allele is a risk factor of CAD also when correcting for conventional risk factors. We found a significant association between the PON1-Arg-192 genotype (QR + RR) and the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel disease with OR = 1.49, P = 0.046; χ2 = 3.82, P = 0.048 and OR = 1.46, P = 0.05; χ2 = 3.48, P = 0.051, respectively. The CAD patients carrying PON1-Arg-192 genotype (QR + RR) had lower plasma HDL-C level (P = 0.019) and higher plasma LDL-C(P = 0.01) and TG(P = 0.05). Our results indicated that PON1-Arg-192 allele can be important independent risk factor of CAD in a west population of Iran, with carriers of PON1-Arg-192 having an increased frequency of three-vessel disease and also having a distinct plasma lipids profile. Larger collaborative studies are needed to confirm these results.


Assuntos
Alelos , Arginina/genética , Arildialquilfosfatase/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Estenose Coronária/complicações , Estenose Coronária/genética , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/enzimologia , Estenose Coronária/sangue , Estenose Coronária/enzimologia , Demografia , Complicações do Diabetes/complicações , Feminino , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
19.
J Cyst Fibros ; 7(2): 102-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17662673

RESUMO

BACKGROUND: Cystic fibrosis (CF) is the most common inherited disorder in Caucasian populations, with over 1400 mutations identified in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Mutations in the CFTR gene may be also causative for CBAVD (Congenital Bilateral Absence of the Vas Deferens). The type and distribution of mutations varies widely between different countries and/or ethnic groups, and is relatively unknown in Iran. We therefore performed a comprehensive analysis of the CFTR gene in Iranian CF patients. METHODS: 69 Iranian CF patients, and 1 CBAVD patient, were analysed for mutations in the complete coding region, and its exon/intron junctions, of their CFTR genes, using different methods, such as ARMS (amplification refractory mutation system)-PCR, SSCP (single stranded conformation polymorphism) analysis, restriction enzyme digestion analysis, direct sequencing, and MLPA (Multiplex Ligation-mediated Probe Amplification). RESULTS: CFTR mutation analysis revealed the identification of 37 mutations in 69 Iranian CF patients. Overall, 81.9% (113/138) CFTR genes derived from Iranian CF patients could be characterized for a disease-causing mutation. The CBAVD patient was found to be homozygous for the p.W1145R mutation. The most common mutations were p.F508del (DeltaF508) (18.1%), c.2183_2184delAAinsG (2183AA>G) (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5G>A (4.3%), p.G542X (3.6%), c.3120+1G>A (3.6%), p.R334W (2.9%) and c.3130delA (2.9%). These 9 types of mutant CFTR genes totaled for 52% of all CFTR genes derived from the 69 Iranian CF patients. Eight mutations, c.406-8T>C, p.A566D, c.2576delA, c.2752-1_2756delGGTGGCinsTTG, p.T1036I, p.W1145R, c.3850-24G>A, c.1342-?_1524+?del, were found for the first time in this study. CONCLUSIONS: We identified 37 CFTR mutations in 69 well characterized Iranian CF patients, obtaining a CFTR mutation detection rate of 81.9%, the highest detection rate obtained in the Iranian population so far. These findings will assist in genetic counseling, prenatal diagnosis and future screening of CF in Iran.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , DNA/genética , Mutação , Adolescente , Criança , Pré-Escolar , Fibrose Cística/epidemiologia , DNA/análise , Análise Mutacional de DNA/métodos , Feminino , Genótipo , Humanos , Lactente , Irã (Geográfico)/epidemiologia , Masculino , Prevalência , Estudos Retrospectivos
20.
Iran J Allergy Asthma Immunol ; 5(1): 3-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17242497

RESUMO

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: deltaF508, N1303K, G542X, 1717-1G>A, R553X, W1282X, G551D, 621+1G>T, deltaI507 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: deltaF508 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.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Adolescente , Substituição de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Irã (Geográfico) , Masculino , Mutação Puntual , Deleção de Sequência
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