Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?
BACKGROUND First considered as a polymorphism of the HFEgene, 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...
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Published in | Gut Vol. 48; no. 6; pp. 836 - 842 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd and British Society of Gastroenterology
01.06.2001
BMJ BMJ Publishing Group LTD |
Subjects | |
Online Access | Get full text |
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Summary: | BACKGROUND First considered as a polymorphism of the HFEgene, 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. AIMS To describe the clinical expression of iron overload (IO) associated with H63D homozygosity, and search for potential genetic modifiers (within theHFE or other genes) that could explain the variability of the phenotypes. PATIENTS AND METHODS We retrospectively analysed the clinical phenotype of 56 H63D homozygotes referred for a personal or family history of IO. For each subject we examined intragenicHFE haplotypes and transferrin receptor (TfR) gene polymorphisms and searched for the Y250X mutation on the TFR2 gene. Additionally, we sequenced theHFE gene of H63D homozygotes with HH. RESULTS Fifty 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 HFEwas identified. CONCLUSION The 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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Bibliography: | PMID:11358905 local:gutjnl;48/6/836 istex:F36A129CA51292D5050BF52264D870C357107DC9 ark:/67375/NVC-XJS4TJCQ-D href:gutjnl-48-836.pdf ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0017-5749 1468-3288 1458-3288 |
DOI: | 10.1136/gut.48.6.836 |