scholarly journals C282Y and H63D Mutation Frequencies in a Population from Central Spain

2001 ◽  
Vol 17 (2) ◽  
pp. 111-114 ◽  
Author(s):  
S. Alvarez ◽  
M. S. Mesa ◽  
F. Bandrés ◽  
E. Arroyo
Keyword(s):  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Epidemiological Data ◽  
Hfe Gene ◽  
Mediterranean Populations ◽  
H63d Mutation ◽  
Pcr Rflp ◽  
Hemochromatosis Gene ◽  
Ethidium Bromide Staining ◽  
Spanish Populations

Objectives:To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula.Methods:DNA extracted from blood samples was analyzed by PCR-RFLP. Restriction enzimes were Snab I and Bcl I for C282Y and H63D, respectively. Results were visualized with Ethidium Bromide staining after gel electrophoresis.Results and discussion:C282Y frequency was 0.02 and that of H63D was 0.16. Result for C282Y mutation falls within the range of variation of the Mediterranean populations. H63D frequency agrees with those reported for other European populations. In both cases frequencies obtained are the lowest of compared Spanish data.Conclusions:This study is useful to compare expected versus presented C282Y and H63D frequencies in Spanish populations and to contribute to the knowledge of Spanish variability, rarely analyzed until now for HFE gene mutations.

Clinical significance of HFE gene mutations in patients with refractory anemia with ring sideroblasts (RARS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18556-e18556
Author(s):  
Rama Nanah ◽  
Mrinal Patnaik ◽  
Naseema Gangat ◽  
Darci Zblewski ◽  
Rong He ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Refractory Anemia ◽  
Heterozygous Mutation ◽  
Hfe Gene ◽  
C282y Mutation ◽  
H63d Mutation ◽  
Ring Sideroblasts ◽  
Hfe Gene Mutations

e18556 Background: RARS is a subtype of myelodysplastic syndromes (MDS) defined by < 5% blasts and ≥15% ring sideroblasts (WHO 2008). Hereditary hemochromatosis is a disorder characterized by dysregulations in iron absorption, largely associated with C282Y and H63D mutations of the HFE gene. Iron levels are elevated in both disorders and pathophysiologic correlations were suggested. HFE gene mutations were previously found higher in MDS compared to controls (50% vs 36%) ( Nearman et al, Am J Hematol 2007). Methods: A total of 168 RARS patients’ data from 1994 to 2015 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our center. We searched patients’ records retrospectively to Identify those tested for HFE gene (C282Y, H62D, S65C) mutations, done inside or outside our institution. Survival estimates were calculated using Kaplan-Meier curves. Results: Out of the 168 RARS patients, only 17 (10%) were tested for HFE gene mutations. Out of the 17 tested, 11 (65%) were found to have mutations; 2 of which (18%) had homozygous H63D mutation, 1 patient (9%) had double heterozygous H63D and C282Y mutations, 5 (45%) had only one H36D heterozygous mutation vs 3 patients (27%) with only one C282Y heterozygous mutation. Only one patient was tested for the additional S65C mutation and it was not detected. H63D mutation was present in a total of 8 patients (73%) vs C282Y mutation which was present in 4 patients (36%). Bone marrow iron stores were increased in all 17 tested patients, except one who had decreased stores, this patient had one heterozygous C282Y mutation. Median overall survival (mOS) was 117 months in the HFE mutated patients vs 75 months in the non-mutated (p = 0.6). Conclusions: Our study found the HFE gene, when tested, to be mutated in higher frequencies among patients with RARS compared to that reported in the general population (65% vs 36%), with H63D mutation in almost three quarters of all mutated patients. Although it did not reach statistical significance, the longer survival observed among HFE mutated patients compared to the wild-type raises the question whether testing for HFE gene mutations among patients with MDS-RARS should be further explored.

scholarly journals Solid-Phase Amplification for Detection of C282Y and H63D Hemochromatosis (HFE) Gene Mutations

2001 ◽  
Vol 47 (8) ◽  
pp. 1384-1389 ◽  
Author(s):  
Mark S Turner ◽  
Sarah Penning ◽  
Angela Sharp ◽  
Valentine J Hyland ◽  
Ray Harris ◽  
...  
Keyword(s):  
Solid Phase ◽  
Point Mutations ◽  
Gene Mutations ◽  
Pcr Primers ◽  
Clinical Samples ◽  
Hfe Gene ◽  
Target Sequence ◽  
Nucleotide Polymorphisms ◽  
Nitrophenyl Phosphate ◽  
Hemochromatosis Gene

Abstract Background: There is a need for simple, rapid, and inexpensive methods for the detection of single-nucleotide polymorphisms. Our aim was to develop a single-tube ELISA-like PCR assay and evaluate it by detecting the common C282Y and H63D mutations found in the hemochromatosis gene (HFE) by use of clinical samples. Methods: The method, termed solid-phase amplification (SPA), involves dual liquid- and solid-phase amplification of a target sequence by the use of two PCR primers, one of which is in two forms: the first is covalently immobilized to the wall of a microwell, and the second is free in solution. During allele-specific amplification, both the free and solid-phase amplicons are labeled by incorporation of digoxigenin (DIG)-dUTP. The amount of surface-bound amplicon is determined colorimetrically by the use of an alkaline phosphatase-anti-DIG-Fab conjugate and p-nitrophenyl phosphate. Results: Two different amplicon-labeling methods were evaluated. Analysis of 173 clinical samples for the C282Y and H63D HFE point mutations with SPA revealed that only one sample was incorrectly diagnosed, apparently because of operator error, when compared with conventional restriction fragment length polymorphism assay results. Conclusions: The SPA assay has potential for medium-scale mutation detection, having the advantage of being manipulatively simple and immediately adaptable for use in clinical laboratories with existing ELISA instrumentation.

scholarly journals Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

2021 ◽  
Vol 8 (4) ◽  
pp. 233-247
Author(s):  
Bhuvana Selvaraj ◽  
◽  
Sangeetha Soundararajan ◽  
Shettu Narayanasamy ◽  
Ganesan Subramanian ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Globin Gene ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Beta Thalassemia ◽  
Hemochromatosis Gene

<abstract> <p>Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with <italic>HFE</italic> gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of <italic>HFE</italic> variants among beta thalassemia cases and their effect on iron overload. The frequency of three <italic>HFE</italic> variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating <italic>HFE</italic> variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C <italic>HFE</italic> variant was absent in the present study. Iron overload was completely absent in the control cases among all three <italic>HFE</italic> genotypes. Hence it is inferred from the present investigation, analysis of <italic>HFE</italic> genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.</p> </abstract>

A NOVEL Mutation of the Erythroid-Specific Aminolevulinate Synthase 2 Gene IN A Patient with Pyridoxine Responsive Sideroblastic Anemia and Deferasirox Responsive Hemochromatosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5105-5105
Author(s):  
Umran Caliskan ◽  
Huseyin Tokgoz ◽  
Hasan Yuksekkaya
Keyword(s):  
Novel Mutation ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Chelating Agent ◽  
Peripheral Blood Smear ◽  
Microcytic Anemia ◽  
Hfe Gene ◽  
Sideroblastic Anemia ◽  
Aminolevulinate Synthase ◽  
Hypochromic Microcytic Anemia

Abstract Abstract 5105 A-14 years-old man, admitted to our clinic with weakness and paleness since one month. He has hepatosplenomegaly. Blood tests and peripheral blood smear showed anemia that severe hypochromic, microcytic anemia. There is ringed sideroblasts without dysplastic hematopoiesis in bone marrow cytology. Liver tests were normal. A liver biopsy showed heavy parenchymal iron deposition and grade-III fibrosis. Screening for HFE gene mutations was negative. MR imaging demonstrated that severe iron accumulation in liver and heart. ALAS2 gene screening showed that novel mutation in exon 7 (Gly390Gly, c.1170, C□T). Eventually, was diagnosed as sideroblastic anemia and hemochromatosis. He was treated successfully with pyridoxine and chelating agent (deferasirox, IGL-670). The findings suggest that the Gly390Gly in ALAS2 mutation causes sideroblastic anemia and hemochromatosis, without hereditary hemochromatosis gene mutations. This mutation cause sideroblastic anemia is clinically pyridoxine-responsive. Deferasirox is effective agent for reduce hepatic iron loading in this condition. Disclosures Off Label Use: deferasiroks was used for hemochromatosis secondary to congenital syderoblastic anemia.

Distribution of HFE gene mutations in Slovenian patients with hereditary hemochromatosis

2008 ◽  
Vol 87 (8) ◽  
pp. 667-669 ◽  
Author(s):  
Srecko Stepec ◽  
Jana Makuc ◽  
Sasa Markovic ◽  
Igor Medica ◽  
Borut Peterlin
Keyword(s):  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Hfe Gene ◽  
Hfe Gene Mutations

Physiology of iron transport and the hemochromatosis gene

2002 ◽  
Vol 282 (3) ◽  
pp. G403-G414 ◽  
Author(s):  
Antonello Pietrangelo
Keyword(s):  
Iron Homeostasis ◽  
Cell Damage ◽  
Hereditary Hemochromatosis ◽  
Hfe Gene ◽  
Cell Functions ◽  
Cellular Iron ◽  
Histocompatibility Complex ◽  
Biological Studies ◽  
Hemochromatosis Gene ◽  
Main Protein

Iron is essential for fundamental cell functions but is also a catalyst for chemical reactions involving free radical formation, potentially leading to oxidative stress and cell damage. Cellular iron levels are therefore carefully regulated to maintain an adequate substrate while also minimizing the pool of potentially toxic “free iron.” The main control of body iron homeostasis in higher organisms is placed in the duodenum, where dietary iron is absorbed, whereas no controlled means of eliminating unwanted iron have evolved in mammals. Hereditary hemochromatosis, the prototype of deregulated iron homeostasis in humans, is due to inappropriately increased iron absorption and is commonly associated to a mutated HFE gene. The HFE protein is homologous to major histocompatibility complex class I proteins but is not an iron carrier, whereas biochemical and cell biological studies have shown that the transferrin receptor, the main protein devoted to cellular uptake of transferrin iron, interacts with HFE. This review focuses on recent advances in iron research and presents a model of HFE function in iron metabolism.

scholarly journals Complete Scanning of the Hereditary Hemochromatosis Gene (HFE) by Use of Denaturing HPLC

2001 ◽  
Vol 47 (9) ◽  
pp. 1633-1640 ◽  
Author(s):  
Gerald Le Gac ◽  
Catherine Mura ◽  
Claude Férec
Keyword(s):  
Hereditary Hemochromatosis ◽  
Hfe Gene ◽  
Test Accuracy ◽  
Melting Profile ◽  
Coding Region ◽  
Hemochromatosis Gene ◽  
Hfe Mutations ◽  
Methods Analytical ◽  
Positive Controls ◽  
Experimental Melting

Abstract Background: Between 4% and 35% of hereditary hemochromatosis (HC) probands are C282Y or H63D heterozygotes or lack both of these two common HFE mutations, and 15 novel HFE mutations have been described recently. We evaluated denaturing HPLC (DHPLC) for screening of the whole HFE coding region and further defined whether HC probands with an incomplete HFE genotype carry uncommon mutations. Methods: Analytical conditions for each coding exon were determined by a combination of computer melting profile predictions and experimental melting curves. To test accuracy for scanning the complete HFE coding region and optimize DHPLC running conditions, each melting domain was investigated with at least one mutation or one polymorphism as reference. We tested 100 DNA samples harboring the C282Y, H63D, or S65C mutations and 17 artificially created positive controls that carried either 1 of the 14 other known HFE mutations or 3 selected polymorphisms. Results: Investigations on each of the coding exons 1, 2, 4, 5, and 6 could be performed at one analysis temperature. Coding exon 3 displayed a more complex melting profile and required two analysis temperatures. DHPLC detected all known HFE mutations as well as the three selected polymorphisms. Conclusions: DHPLC can be used to scan the HFE gene in HC probands in whom at least one chromosome lacks an assigned mutation.

scholarly journals Hemochromatosis: one form of iron-overload diseases

2013 ◽  
Vol 154 (29) ◽  
pp. 1156-1164 ◽  
Author(s):  
Ferenc Szalay
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Clinical Symptoms ◽  
Fetal Liver ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Organ Injury ◽  
Beta Thalassemia ◽  
Hfe Gene ◽  
Kinase Gene

Iron-overload diseases are typically insidious, causing progressive and irreversible organ injury before clinical symptoms develop. Some iron-overload diseases as HFE-associated hemochromatosis and beta-thalassemia are quite common, whereas others are very rare. Early diagnosis is important since iron toxicity can be attenuated or prevented. Significant progress of our knowledge on iron metabolism developed in the past years. We learned a lot about HFE gene mutations, function of ferroportin and hepcidin, the hypoferremia hormone produced by the liver. However, many questions are still open. Special forms of localized iron overload are the Hallervorden-Spatz syndrome and pantothenate kinase gene mutation associated neurodegeneration causing progressive extrapyramidal movement disorders. Neonatal hemochromatosis is a severe systemic iron-overload disorder due to gestational alloimmune liver disease caused by transplacental maternal IgG directed against the fetal liver. This review article gives an overview on iron metabolism and iron-overload disease. Pathomechanism, diagnosis and treatment of hereditary hemochromatosis are discussed. Orv. Hetil., 2013, 154, 1156–1164.

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