In-silico Molecular Analysis of Mutated Sequences of HFE1, HFE2, TFR2 and SLC40A1 causing Hemochromatosis Disease (original) (raw)
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Mutations of the HFE gene among Turkish hereditary hemochromatosis patients
Annals of Hematology, 2005
Since the discovery of the HFE gene, C282Y and H63D mutations have been reported as significantly correlated with clinically manifested hereditary hemochromatosis (HH). As the other genes involved in iron metabolism have been described, non-HFE cases of HH have been identified. Since in the general Turkish population, the C282Y mutation is not found and the H63D mutation is of high frequency, we aimed to determine mutations in the HFE genes in our patients with HH. The HFE gene of the five patients with HH were sequenced. C282Y mutation was absent, and all HH patients were heterozygote for H63D mutation. No other mutation was found in HFE gene by sequencing. Although the higher allele frequency of the H63D mutation in Turkish HH patients than in the general population implies a role of the H63D mutation in iron overload, there is a strong possibility that Turkish HH patients have non-HFE hemochromatosis.
The National medical journal of India
Primary haemochromatosis is characterized by iron overload in the body tissues. It is common in populations of northern European descent. In such populations, 85%-90% of patients with this disease have a C282Y mutation in the HFE gene. In India, the disease is uncommon and the genetic defects associated with it are unknown. We therefore looked for mutations in the HFE and other genes involved in iron metabolism in Indian patients with primary haemochromatosis. Five patients (including a brother-sister pair) with primary haemochromatosis diagnosed on clinical, biochemical and histological findings were studied. Genomic DNA was analysed by sequencing for the presence of mutations in all the 6 exons of the HFE gene and for previously described mutations in genes encoding hepcidin antimicrobial peptide and ferroportin. No patient had the C282Y mutation. One had homozygous H63D mutation. No other mutation was found in any HFE exon. Two previously reported splice site mutations in the HFE...
Saudi Medical Journal, 2019
Objectives: To evaluate any association between the frequency of hereditary hemochromatosis (HFE) gene mutation)H63D and C282Y(and iron overload in betathalassemia major)BTM(patients. Methods: The case-control study was conducted from June 2016 to February 2018. Blood samples from 204 BTM patients and 204 normal controls were taken from the Sundas Foundation Blood Bank. Original Articles These samples were analyzed for serum ferritin assay and HFE mutation. Ferritin level was measured on the ARCHITECT 1000SR. Both patient and control samples were analyzed for mutations using polymerase chain reaction-restriction fragment length polymorphism)PCR-RFLP(. Results: Serum ferritin levels for all patients were >1000ng/mL. The p.H63D mutation was observed in 23)11.3%(cases, out of which 19 cases were heterozygous for p.H63D and 4 cases were homozygous. In control samples, 4 cases)2%(were found heterozygous for the p.H63D, and no homozygous mutation was found. Significantly high serum ferritin levels were found in BTM patients with the H63D mutation)p=0.00(. In the case of p.C282Y, neither homozygous nor heterozygous mutation was found in patients or in controls. Conclusion: H63D polymorphism is associated with iron overload in BTM patients. Larger-scale research is required to give an elaborated view of the association of the HFE mutation with iron overload in these patients and to confirm our conclusion.
Hereditary Hemochromatosis: The Role of Proteins in Iron Homeostasis
International Journal of Health Science, 2023
Iron is an essential mineral for organic activities, and inadequate levels cause pathologies. A lack of it leads to iron deficiency anemia, whereas excess leads to hemochromatosis, which is a disease caused by excessive accumulation of iron, mainly in the liver. There are two types of hemochromatosis: acquired, which is caused by excessive iron intake or multiple blood transfusions, and hereditary, caused by mutations in the HFE gene, which lead to reduced hepcidin synthesis and consequent excessive iron absorption by the intestines. This accumulation of iron in the body leads to harmful consequences, such as liver cirrhosis, diabetes mellitus, atrophy, and myocardial dysfunction, among others. In both types of hemochromatosis, and especially in hereditary hemochromatosis, some proteins play a fundamental role in iron absorption and metabolism, with highlight to hepcidin. The present literature review aims to study hemochromatosis characteristics and the functions of proteins, especially hepcidin, in iron homeostasis.
Mutations in HFE and TFR2 genes in a Spanish patient with hemochromatosis
Revista Espanola De Enfermedades Digestivas, 2011
Iron overload disease has a wide variety of genotypes. The genetic study of this disease confirms its hereditary nature and enables us to provide genetic counseling for first-degree relatives. We performed magnetic resonance imaging and liver biopsy in an asymptomatic patient with more than 1,000 µg/L of serum ferritin and studied the genes involved in this condition. The phenotype of iron overload is confirmed by a predominantly periportal pattern of iron deposits in the liver suggestive of genetic disease. In the case we present the molecular study revealed a double heterozygosity for the mutations c.187C>G (p.H63D) and c.840C>G (p.F280L) in the HFE and transferrin receptor 2 (TFR2) genes, respectively.
Hemochromatosis gene (HFE) mutations in South East Asia: a potential for iron overload☆
Blood Cells, Molecules, and Diseases, 2003
Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by mutations in the HFE gene that mainly affects populations of European descent. Recently a novel mutation (IVS5ϩ1 G3 A) has been described in a Vietnamese patient with HH that was not detected in a European control population. We have developed a novel method to screen for this mutation based on restriction enzyme digestion of a PCR product using a modified forward primer. We have screened 314 Vietnamese people from several ethnic groups and 154 people from Thailand for this mutation and have detected two heterozygotes in the Vietnamese subjects (allele frequency 0.003). Analysis of these heterozygotes indicates that the mutation is on the same haplotype as that found in the original proband. Screening for the widely distributed HFE mutation, H63D, gave an allele frequency of 0.049 in the Vietnamese subjects and 0.032 in the subjects from Thailand. This is the first report of H63D allele frequencies in these populations. We suggest that the presence of the IVS5ϩ1 G3 A and H63D mutations should be considered when investigating iron overload in Vietnamese patients and those of mixed origin as co-inheritance of both mutations is likely to be a risk factor for iron overload.
Hereditary Hemochromatosis Since Discovery of the HFE Gene
Clinical Chemistry, 2001
Background: Hereditary hemochromatosis is an inherited disorder of iron metabolism that is characterized by excessive iron deposition in major organs of the body. Chronic increased iron absorption leads to multiorgan dysfunction. Since the discovery of the gene responsible for the majority of cases, research has progressed rapidly to identify the gene product, the effects of mutations, and the implications for different populations. The protein product of the HFE gene is a transmembrane glycoprotein, termed HFE, that modulates iron uptake. Mutations in the HFE protein compromise its function and produce disease symptoms. Two mutations, C282Y and H63D, have been linked to the majority of disease cases. Approach: We reviewed the recent literature for the molecular basis of hereditary hemochromatosis. Genotypic information was combined with biochemical and clinical phenotypic information to achieve a better understanding of the disease mechanism. Content: This review provides a compreh...