Polymorphisms in the HFE Gene

Douabin, V.; Moirand, Romain; Jouanolle, Anne–Marie; Brissot, Pierre; Gall, J. Y. Le; Deugnier, Yves; David, Véronique

doi:10.1159/000022835

Cited by 36 publications

(18 citation statements)

References 14 publications

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“…The isolated nature of this finding is concordant with previous studies of TfR2 12,[21][22] or HFE 15,23 in non-C282Y homozygous HH. However, the identification of the TfR2 Q690P mutation helps to establish TfR2 mutations as infrequent but important contributors to autosomal recessive adult-onset HH.…”

Section: Resultssupporting

confidence: 92%

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation

Mattman

2002

Blood

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Section: Resultssupporting

confidence: 92%

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation

Mattman

2002

Blood

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“…This transversion is a recently reported polymorphism that results in a serine-to-cysteine amino acid substitution at codon 65 (S65C). 22 The S65C polymorphism creates an A:A mismatch located 8 bp in from the 3Ј end of the 27-mer probe (see Figure 1 and Table 1). When the probe hybridizes to an allele that is wild type at the H63D site but contains the S65C polymorphism, two mismatches are present.…”

Section: Genotyping With Adjacent Fluorescent Hybridization Probesmentioning

confidence: 99%

Homogeneous Multiplex Genotyping of Hemochromatosis Mutations with Fluorescent Hybridization Probes

Bernard¹,

Ajioka²,

Kushner³

et al. 1998

The American Journal of Pathology

146

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Multiplex polymerase chain reaction amplification and genotyping by fluorescent probe melting temperature (T m ) was used to simultaneously detect multiple variants in the hereditary hemochromatosis gene. Homogenous real-time analysis by fluorescent melting curves has previously been used to genotype single base mismatches; however , the current method introduces a new probe design for fluorescence resonance energy transfer and demonstrates allele multiplexing by T m for the first time. The new probe design uses a 3-fluorescein-labeled probe and a 5-Cy5-labeled probe that are in fluorescence energy transfer when hybridized to the same strand internal to an unlabeled primer set. Two hundred and fifty samples were genotyped for the C282Y and H63D hemochromatosis causing mutations by fluorescent melting curves. Multiplexing was performed by including two primer sets and two probe sets in a single tube. In clinically defined groups of 117 patients and 56 controls , the C282Y mutation was found in 87% (204/ 234) of patient chromosomes , and the relative penetrance of the H63D mutation was 2.4% of the homozygous C282Y mutation. Results were confirmed by restriction enzyme digestion and agarose gel electrophoresis. In addition , the probe covering the H63D mutation unexpectedly identified the A193T polymorphism in some samples. This method is amenable to multiplexing and has promise for scanning unknown mutations. (Am J Pathol 1998, 153:1055-1061)

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“…Eighty to 90% of patients with Hereditary Hemochromatosis show the C282Y mutationvariant, especially in homozygosity, and 3 to 5% are compound heterozygotes between C282Y and H63D [96]. Another mutation on the exon 2 of the HFE locus, the S65C, a A-to-T transition at the position 193 that leads to a serine-to-cysteine substitution, have been shown to be associated with milder iron overload [107,118] The product of the HFE locus is a transmembrane glycoprotein that is thought to regulate iron uptake through a mechanism that involves its binding to the transferrin receptor in the cell membrane [9]. The mutation C282Y described above, when inherited in homozygosity or in compound heterozygosity with other mutations, could increase iron uptake leading to the development of Hereditary Hemochromatosis.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal)

2010

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Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that result from mutations in the HFE gene. Almost all patients with Hereditary Hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to Hereditary Hemochromatosis. One hundred and fifty four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y and S65C, by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33% and 1% for H63D, C282Y and S65C, respectively. Accordingly to our estimates, both genotypes associated to Hereditary Hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.Response to Reviewers: . In this revised version we included the four references recommended by reviewers: Reviewer #1: The introduction to a large extent repeats well known facts about HFE hemochromatosis and should be shortened at least by 3/4 page. Authors: we shortened the introduction.Reviewer #1: There are several spelling errors. Authors: We made a spelling revision.Reviewer #1: In recent years, Annals of Hematology has published many papers on HFE haemochromatosis, among others by the authors Remacha AF, Pedersen P, Milman N, ect. I strongly suggest the authors make a screening on PubMed to identify these AOH papers and include them in the reference list. Authors: We added a paper from Remacha published in Annals of Hematology.

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Polymorphisms in the HFE Gene

Cited by 36 publications

References 14 publications

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation

Homogeneous Multiplex Genotyping of Hemochromatosis Mutations with Fluorescent Hybridization Probes

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal)

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