Abstract
Background/Aims: HFE-related haemochromatosis is a common disorder of iron metabolism. Most affected individuals
are homozygous for the C282Y mutation of HFE. Some are compound heterozygotes for C282Y/H63D. A small proportion have neither
of these genotypes. We have investigated the phenotype of compound heterozygotes for
C282Y and another missense mutation S65C.
Methods: Genotype for the S65C mutation was determined in 309 subjects heterozygous for C282Y
and negative for H63D, referred because of increased serum iron indices or family
screening. A control sample comprising 315 individuals was also studied.
Results: Twelve individuals were compound heterozygotes for C282Y and S65C. Seven, referred
for family screening, had normal serum iron indices. Five subjects had elevated serum
iron indices; three of these had elevated hepatic iron and have received treatment
for iron overload. Transferrin saturation was significantly elevated in C282Y/S65C
compound heterozygotes compared with simple C282Y heterozygotes.
Conclusions: Some C282Y/S65C compound heterozygotes have elevated serum iron indices and iron
overload. The penetrance of this genotype is low and other genetic and environmental
factors may influence the expression of iron loading. Screening for S65C may be useful
in individuals with iron overload who are not homozygous for C282Y or compound heterozygous
for C282Y/H63D.
Keywords
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References
- A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.Nat Genet. 1996; 13: 399-408
- Uncommon mutations and polymorphisms in the hemochromatosis gene.Genet Test. 2000; 4: 151-161
- A novel mutation of HFE explains the classical phenotype of genetic hemochromatosis in a C282Y heterozygote.Gastroenterology. 1999; 116: 1409-1412
- Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands.Blood Cells Mol Dis. 1999; 25: 146-154
- Screening for haemochromatosis in Switzerland: detection of a new pathogenic mutation and two additional variants in exon 2 of the HFE gene.Eur J Hum Genet. 1999; 7: 122
- Two novel nonsense mutations of HFE gene in five Italian patients with hemochromatosis.Gastroenterology. 2000; 119: 441-445
- HLA-H gene mutations and haemochromatosis: the likely association of H63D with mild phenotype and the detection of S65C, a novel variant of exon 2.J Hepatol. 1997; 26: 57
- HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis.Blood. 1999; 93: 2502-2505
- HFE S65C variant is not associated with increased transferrin saturation in voluntary blood donors.Blood Cells Mol Dis. 1999; 25: 354-357
- Commentary on HFE S65C variant is not associated with increased transferrin saturation in voluntary blood donors by Naveen Arya, Subrata Chakrabrati, Robert A. Hegele, Paul C. Adams.Blood Cells Mol Dis. 1999; 25: 358-360
- A simple genetic test identifies 90% of UK patients with haemochromatosis.Gut. 1997; 41: 841-844
- Polymorphisms in the HFE gene.Hum Hered. 1999; 49: 21-26
- Identification of homozygous hemochromatosis subjects by measurement of hepatic iron index.Hepatology. 1990; 12: 20-25
- Diagnosis and management of hemochromatosis.Hepatology. 2001; 33: 1321-1328
- The significance of the 187G (H63D) mutation in hemochromatosis.Am J Hum Genet. 1997; 61: 762-764
- Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor.Cell. 1998; 93: 111-123
- The effects of wild-type and mutant HFE expression upon cellular iron uptake in transfected human embryonic kidney cells.Biochim Biophys Acta. 2001; 1538: 242-251
- Juvenile hemochromatosis locus maps to chromosome 1q.Am J Hum Genet. 1999; 64: 1388-1393
- A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis.Nat Genet. 2001; 28: 213-214
- Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene.J Clin Invest. 2001; 108: 619-623
- The gene TfR2 is mutated in a new type of hemochromatosis mapping to 7q22.Nat Genet. 2000; 25: 14-15
- A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload.Am J Hum Genet. 2001; 69: 191-197
Article info
Publication history
Accepted:
November 28,
2001
Received in revised form:
November 23,
2001
Received:
July 18,
2001
Identification
Copyright
© 2002 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
