Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload
Date
2004
Authors
Zaahl M.G.
Merryweather-Clarke A.T.
Kotze M.J.
van der Merwe S.
Warnich L.
Robson K.J.H.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Extensive investigation into the molecular basis of iron overload disorders has provided new insights into the complexity of iron metabolism and related cellular pathways. The possible involvement of genes affecting iron homeostasis, including HFE, SLC40A1, HAMP and CYBRD1, was investigated in individuals who were referred for confirmation or exclusion of a diagnosis of haemochromatosis, but who tested negative or were heterozygous for the causative HFE mutation, C282Y. Denaturing high performance liquid chromatography analysis of these genes revealed a unique spectrum of mutations in the South African study population, including 67 unrelated patients and 70 population-matched controls. Two novel CYBRD1 gene mutations, R226H and IVS1-4C→G, were identified in 11% of South African Caucasian patient referrals. We identified a novel D270V mutation in the SLC40A1 gene in a Black South African female with iron overload. These mutations were absent in the control population. In Africans with iron overload not related to the HFE gene, the possible involvement of the SLC40A1 and CYBRD1 genes was demonstrated for the first time. This study confirms the genetic heterogeneity of haemochromatosis and highlights the significance of CYBRD1 mutations in relation to iron overload. © Springer-Verlag 2004.
Description
Keywords
hepcidin, HFE protein, iron, natural resistance associated macrophage protein 2, article, Caucasian, controlled study, gene mutation, genetic heterogeneity, hemochromatosis, heterozygosity, high performance liquid chromatography, human, iron metabolism, iron overload, major clinical study, patient referral, population research, priority journal, regulatory mechanism, South Africa, Adult, African Continental Ancestry Group, Case-Control Studies, Cation Transport Proteins, Cytochrome b Group, European Continental Ancestry Group, Female, Hemochromatosis, Histocompatibility Antigens Class I, Humans, Iron, Iron Overload, Membrane Proteins, Molecular Sequence Data, Mutation, Oxidoreductases, Polymorphism, Genetic, Variation (Genetics)
Citation
Human Genetics
115
5
115
5