ArticleGut2001
Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?
Article in Gut, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH).European journal of human genetics : EJHG · 2016Guideline
- Genetic history of Scythia.Science advances · 2025Article
- H63D Homozygous Mutation: An Unusual Cause of Deranged Liver Function Test in an Elderly Patient.Cureus · 2022Article
- HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity.Hereditas · 2022Article
- Article
- Haemochromatosis.Nature reviews. Disease primers · 2018Review
- HFE Variants and the Expression of Iron-Related Proteins in Breast Cancer-Associated Lymphocytes and Macrophages.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2016Article
- Genetic variant coding for iron regulatory protein HFE contributes to hypertension, the TAMRISK study.Medicine · 2015Article
- Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.Brain imaging and behavior · 2014Review
- Iron overload is rare in patients homozygous for the H63D mutation.Canadian journal of gastroenterology & hepatology · 2014Article
- Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance.Haematologica · 2010Article
- HAMP promoter mutation nc.-153C>T in non p.C282Y homozygous patients with iron overload.Haematologica · 2010Article
- The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins.BMC gastroenterology · 2010Article
- HFE gene mutations, serum ferritin level, transferrin saturation, and their clinical correlates in a Korean population.Digestive diseases and sciences · 2009Article
- Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis.Clinics (Sao Paulo, Brazil) · 2009Article
- New HJV mutation in a patient with hyperferritinemia and H63D homozygosity for the HFE gene.International journal of hematology · 2007Article
- HFE gene in primary and secondary hepatic iron overload.World journal of gastroenterology · 2007Review
- A diagnostic approach to hemochromatosis.Canadian journal of gastroenterology = Journal canadien de gastroenterologie · 2006Review
- Individuals homozygous for the H63D mutation have significantly elevated iron indexes.Digestive diseases and sciences · 2006Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFirst considered as a polymorphism of the HFE gene, the H63D mutation is now widely recognised as a haemochromatosis associated allele. But few H63D homozygotes with clinical manifestations of hereditary haemochromatosis (HH) have been reported. Concurrently, an increasing number of genes have been shown to interact with HFE in iron metabolism.
aimsTo describe the clinical expression of iron overload (IO) associated with H63D homozygosity, and search for potential genetic modifiers (within the HFE or other genes) that could explain the variability of the phenotypes. PATIENTS AND
methodsWe retrospectively analysed the clinical phenotype of 56 H63D homozygotes referred for a personal or family history of IO. For each subject we examined intragenic HFE haplotypes and transferrin receptor (TfR) gene polymorphisms and searched for the Y250X mutation on the TFR2 gene. Additionally, we sequenced the HFE gene of H63D homozygotes with HH.
resultsFifty of 56 subjects had biological and/or clinical abnormalities of iron metabolism. Up to two thirds of patients (n=34) had no acquired cause of IO. Among these, 12 had a phenotypic diagnosis of HH. In the iron loaded group there was a strong prevalence of male patients. No correlation was found between the potential genetic modifiers and phenotypes. No additional mutation of HFE was identified.
conclusionThe variable phenotypes associated with H63D homozygosity do not appear to be linked to other HFE mutations, to the TFR2 Y250X mutation, or to HFE or TfR gene intragenic polymorphisms. The exact role of H63D homozygosity in IO and HH needs to be further investigated in unselected populations.
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