Analysis of Iranian patients allowed the identification of the first truncating mutation in the fibrinogen Bbeta-chain gene causing afibrinogenemia.
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BACKGROUND AND OBJECTIVES: Congenital afibrinogenemia is a rare coagulation disorder whose molecular basis is still poorly characterized. Most mutations have been identified in the fibrinogen Aalpha- and gamma-chain genes, whereas only two missense mutations have been reported in the Bbeta-chain gene. The aim of this work was to widen knowledge about the mutational spectrum of this disease by analyzing the molecular bases of congenital afibrinogenemia in three unrelated Iranian patients. DESIGN AND METHODS: All patients showed unmeasurable levels of clottable fibrinogen in plasma. Mutational screening was performed by sequencing the whole coding region, including exon-intron boundaries and part of the promoter region of the three fibrinogen genes. RESULTS: Sequencing in one patient revealed the presence of a novel nonsense mutation (3282C-->T) in exon 2 of the fibrinogen Bbeta-chain gene, causing a severe truncation of the corresponding polypeptide (R17X). In the remaining probands, two already known small deletions (4209delA and 4220delT), both located in exon 5 of the fibrinogen Aalpha-chain gene, were identified, and their effect at the protein level explored by computer-assisted analysis. INTERPRETATION AND CONCLUSIONS: The identification of the first truncating mutation in the fibrinogen Bbeta-chain gene confirms the involvement of all three fibrinogen genes in the pathogenesis of congenital afibrinogenemia and widens the mutational spectrum of the disease. This knowledge is clinically essential in order to carry out prenatal diagnosis in families at risk. (+info)
Lung function values in healthy non-smoking urban adults in iran.
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BACKGROUND: The values of lung function tests (LFTs) are dependent on height, age, and sex. In addition, there is evidence of LFT variation in different ethnic groups. OBJECTIVE: We have therefore derived prediction equations for LFTs from a healthy, non-smoking, urban adult population in the city of Mashhad (northeast Iran). METHODS: Predicted equations for normal lung function have been derived from 572 healthy, non-smoking subjects including 326 men (height 154-195 cm) and 246 women (height 144-174 cm) aged 18-65 years. The subjects underwent measurement of spirometric flow and volume. The following variables were measured: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), maximal mid-expiratory flow (MMEF), peak expiratory flow (PEF) and maximal expiratory flow at 75, 50 and 25% of the FVC (MEF(75), MEF(50), and MEF(25), respectively). Regression analysis using height and age as independent variables was applied to provide predicted values for both sexes. RESULTS: There was a negative correlation between each lung function and age. The largest negative correlations were found for FEV(1) and FVC in men and women, respectively. All parameters correlated positively with height; the largest positive correlation was observed for FVC in both sexes. Comparison of LFTs derived from the equations of the present study showed significant differences with those of several previous studies. CONCLUSION: In this study, a set of LFT reference values and prediction equations for both sexes have been derived using a relatively large, healthy, non-smoking Iranian, adult population which was different from several other prediction equations. (+info)
Risk factors for breast cancer in Iran: a case-control study.
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BACKGROUND: Iranian breast cancer patients are relatively younger than their Western counterparts. The objective of the present study was to investigate risk factors for breast cancer in Iranian women. METHOD: A case-control study was conducted from April 1997 to April 1998 in Tehran, Iran. Demographical data and risk factor related information were collected using a short structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression analysis. RESULTS: In all, 286 women with breast cancer and 249 control women were interviewed. In multivariate analysis, only marital status (never married: OR 4.24, 95% CI 1.70-10.57 [P = 0.002]; widowed/divorced: OR 1.71, 95% CI 1.05-2.68 [P = 0.03]) and family history (positive family history of breast cancer: OR 2.95, 95% CI 1.15-7.59 [P = 0.02]) were associated with significantly increased risk for breast cancer. CONCLUSION: The findings of the present study suggest that family history and marital status may have an impact on the incidence of breast cancer in Iranian women. (+info)
Obesity in Iranian children.
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We surveyed 4315 2-5 year olds in Iran. Prevalence of obesity (BMI >95th centile, Iranian reference data) was compared with the recent "IOTF" approach. Prevalence was significantly higher than expected, and increased with age, but contradictory trends were obtained from the two approaches. Monitoring of childhood obesity using the BMI in developing countries is indicated, but differences associated with obesity definition should be considered. (+info)
Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta-chain gene causing activation of cryptic splice sites.
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Congenital afibrinogenemia is a rare inherited coagulopathy, characterized by very low or unmeasurable plasma levels of immunoreactive fibrinogen. So far, 25 mutations have been identified in afibrinogenemia, 17 in the Aalpha, 6 in the gamma, and only 2 in the Bbeta fibrinogen-chain genes. Here, 2 afibrinogenemic probands, showing undetectable levels of functional fibrinogen, were screened for causative mutations at the genomic level. Sequence analysis of the 3 fibrinogen genes disclosed 2 novel homozygous mutations in introns 6 and 7 of the Bbeta-chain gene (IVS6 + 13C > T and IVS7 + 1G > T), representing the first Bbeta-chain gene splicing mutations described in afibrinogenemia. The IVS6 + 13C > T mutation predicts the creation of a donor splice site in intron 6, whereas the IVS7 + 1G > T mutation causes the disappearance of the invariant GT dinucleotide of intron 7 donor splice site. To analyze the effect of these mutations, expression plasmids containing Bbeta-chain minigene constructs, either wild-type or mutant, were transfected in HeLa cells. Assessed by semiquantitative analysis of reverse transcriptase-polymerase chain reaction products, the IVS7 + 1G > T mutation resulted in multiple aberrant splicings, while the IVS6 + 13C > T mutation resulted in activation of a new splice site 11 nucleotides downstream of the physiologic one. Both mutations are predicted to determine protein truncations, supporting the importance of the C-terminal domain of the Bbeta chain for fibrinogen assembly and secretion. (+info)
Finding genetic contributions to sporadic disease: a recessive locus at 12q24 commonly contributes to patent ductus arteriosus.
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The causes of many sporadic diseases are unexplained; the contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. We describe an approach to this problem by first searching for diseases with higher prevalence in populations with high rates of consanguinity, then determining whether disease cases are more commonly the product of consanguinous union than controls in such populations, followed by analysis of genetic linkage in consanguinous cases. We demonstrate the utility of this approach by investigation of congenital heart disease in Iran. We found that patent ductus arteriosus (PDA), a common congenital heart disease, accounts for a higher fraction of congenital heart disease in Iran (15%) than in the United States (2-7%). Moreover, Iranian PDA cases demonstrated a marked increase of parental consanguinity (63%), compared with the general Iranian population (25%) or control cases with tetralogy of Fallot (30%). The recurrence of PDA among siblings was 5%. A genomewide analysis of linkage in 21 unrelated consanguinous PDA cases demonstrated a multipoint logarithm of odds score of 6.27 in favor of linkage of PDA to a 3-centimorgan interval of chromosome 12q24, with 53% of kindreds linked. These findings together establish a recessive component to PDA and implicate a single locus, PDA1, in one third or more of all PDA cases in Iran; they further suggest a role for this locus in PDA worldwide. Finally, these results suggest a general approach to the identification of recessive contributions to sporadic diseases. (+info)
Dietary factors and esophageal cancer in the Caspian Littoral of Iran.
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A study was undertaken to attempt to relate the distribution of exogenous factors to the varying incidences of esophageal cancer in the Caspian Littoral of Iran. For the study, 38 villages were chosen by random sampling in 14 regions defined by their esophageal cancer incidence and environmental characteristics. Information was obtained on the dietary, social, and cultural features of each village. In addition, an extensive 5-day study of 6 randomly selected households in each of the 38 villages was conducted. The study consisted of measured dietary intake, a historical food consumption questionnaire, and clinical examinations of adult occupants. Preliminary results show no single factor responsible for the etiology of esophageal cancer. However, there were some major dietary differences between the regions of different esophageal cancer risk. Bread was the chief staple food in high-incidence areas; rice, in low-incidence areas. In high-incidence areas, there was a low intake of vitamins A and C, riboflavin, animal protein, and fresh vegetables and fruit, but a greater consumption of sheeps and goat's milk. Analyses of food samples for aflatoxins, polycylic aromatic hydrocarbons, and nitrosamines showed low levels of these carcinogens in areas of high and low incidences. The use of tobacco and alcohol was not found to be of significance. (+info)
Characteristics of gonorrhoea in Kermanshah, Iran.
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OBJECTIVE: To describe the characteristics of gonorrhoea and prostitution in Kermanshah, Iran. METHOD: From 1997 through 2000, 100 male gonorrhoea patients were followed for a mean of 18 months (range 8-42 months). Diagnosis and follow up were made by a combination of history, physical examination, and the Gram stained smear. RESULTS: 4% of patients became infected by girlfriends, 24% by temporary (sigheh) wives, and 64% by street prostitutes; the remaining 8% denied coitus with sex workers. Of 38 married cases, 31 reported unprotected intercourse with permanent wives while infected, and only four of 38 gave prescribed drugs to their wives. 89% of contacts with prostitutes were unprotected. Most of the prostitutes and professional sigheh wives were practising survival sex. Fear of stigmatization and presumed severe penalties prevented prostitutes from seeking medical care, and 26% of patrons reported self medication. An average 84% of prescriptions of standard therapies failed. 31% of the cases remained refractory to all available therapies. CONCLUSIONS: The majority of the prostitutes and sigheh wives in Iran exchange sex for survival. Being uneducated survival sex workers, they accept risky sex behaviours easily. Sigheh wives are an important source of infection. The very high rate of persistent infection despite standard treatments is disturbing. Our ideal is a world in which nobody is obliged to enter commercial sex work. In the meantime, however, there is an urgent need to offer medical care and education to sex workers as needy patients in a safe and unprejudiced environment. Denying the presence of such realities as prostitution and sexually transmitted diseases (STDs) because of their disagreement with cant claims and official propaganda, does not eradicate the facts but results in catastrophic public health problems. (+info)