DOI: 10.1182/blood.v93.8.2502. HFE Mutations Analysis in 711 Hemochromatosis Probands: Evidence for S65C Implication in Mild Form of Hemochromatosis

HFE Mutations Analysis in 711 Hemochromatosis Probands: Evidence for S65C Implication in Mild Form of Hemochromatosis

10.1182/blood.v93.8.2502

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

Abstract Hereditary hemochromatosis (HH) is a common autosomal recessive genetic disorder of iron metabolism. The HFE candidate gene encoding an HLA class I-like protein involved in HH was identified in 1996. Two missense mutations have been described: C282Y, accounting for 80% to 90% of HH chromosomes, and H63D, which is associated with a milder form of the disease representing 40% to 70% of non-C282Y HH chromosomes. We report here on the analysis of C282Y, H63D, and the 193A→T substitution leading to the S65C missense substitution in a large series of probands and controls. The results confirm that the C282Y substitution was the main mutation involved in hemochromatosis, accounting for 85% of carrier chromosomes, whereas the H63D substitution represented 39% of the HH chromosomes that did not carry the C282Y mutation. In addition, our screening showed that the S65C substitution was significantly enriched in probands with at least one chromosome without an assigned mutation. This substitution accounted for 7.8% of HH chromosomes that were neither C282Y nor H63D. This enrichment of S65C among HH chromosomes suggests that the S65C substitution is associated with the mild form of hemochromatosis.

Bibliography

Mura, C., Raguenes, O., & FeÌrec, C. (1999). HFE Mutations Analysis in 711 Hemochromatosis Probands: Evidence for S65C Implication in Mild Form of Hemochromatosis. Blood, 93(8), 2502â2505.

Authors 3

Catherine Mura (first)
Odile Raguenes (additional)
Claude Férec (additional)

References 23 Referenced 269

10.1056/NEJM198805263182103 / N Engl J Med / Prevalence of hemochromatosis among 11065 presumably healthy blood donors. by Edwards (1988)
10.1111/j.1365-2141.1990.tb06345.x / Br J Haematol / Prevalence of haemochromatosis among asymptomatic Australians. by Leggett (1990)
10.1038/ng0896-399 / Nat Genet / A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. by Feder (1996)
10.1074/jbc.272.22.14025 / J Biol Chem / The hemochromatosis founder mutation in HLA-H disrupts β2-microglobulin interaction and cell surface expression. by Feder (1997)
10.1073/pnas.94.6.2534 / Proc Natl Acad Sci USA / Immunochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract. by Parkkila (1997)
10.1073/pnas.94.24.13198 / Proc Natl Acad Sci USA / Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. by Parkkila (1997)
10.1073/pnas.95.4.1472 / Proc Natl Acad Sci USA / The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. by Feder (1998)
10.1073/pnas.95.5.2492 / Proc Natl Acad Sci USA / HFE gene knockout produces mouse model of hereditary hemochomatosis. by Zhou (1998)
10.1038/ng1196-249 / Nat Genet / Haemochromatosis and HLA-H. by Jazwinska (1996)
10.1038/ng1196-251 / Nat Genet / Haemochromatosis and HLA-H. by Jouanolle (1996)
{'key': '2020021216203290500_B11', 'first-page': '828', 'article-title': 'Mutation analysis of the HLA-H gene in Italian hemochromatosis patients.', 'volume': '60', 'author': 'Carella', 'year': '1997', 'journal-title': 'Am J Hum Genet'} / Am J Hum Genet / Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. by Carella (1997)
10.1006/bcmd.1996.0027 / Blood Cells Mol Dis / Mutation analysis in hereditary hemochromatosis. by Beutler (1996)
10.1007/s004390050628 / Hum Genet / Phenotype-genotype correlation in haemochromatosis patients. by Mura (1997)
10.1038/ng1297-375 / Nat Genet / Haemochromatosis, HFE and genetic complexity. by Risch (1997)
10.1073/pnas.94.23.12384 / Proc Natl Acad Sci USA / Hereditary hemochromatosis: Effects of C282Y and H63D mutations on association with β2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. by Waheed (1997)
10.1007/s002510050211 / Immunogenetics / Mutations in the MHC class I-like candidate gene for hemochromatosis in French patients. by Borot (1997)
10.1016/S0002-9297(07)64339-0 / Am J Hum Genet / The significance of the 187G (H63D) mutation in hemochromatosis. by Beutler (1997)
10.1007/BF03401686 / Mol Med / HLA-H and associated proteins in patients with hemochromatosis. by Beutler (1997)
{'key': '2020021216203290500_B19', 'first-page': '268', 'volume-title': 'A single nucleotide deletion in the putative haemochromatosis gene in a patient who is negative for both the C282Y and H63D mutations. International Symposium Iron in Biology and Medicine. Saint-Malo, France', 'author': 'Pointon', 'year': '1997'} / A single nucleotide deletion in the putative haemochromatosis gene in a patient who is negative for both the C282Y and H63D mutations. International Symposium Iron in Biology and Medicine. Saint-Malo, France by Pointon (1997)
10.1006/mcpr.1997.0102 / Mol Cell Probes / Hereditary hemochromatosis: A HpaI polymorphism within the HLA-H gene. by Totaro (1997)
{'key': '2020021216203290500_B21', 'first-page': '267', 'volume-title': 'Polymorphisms in the haemochromatosis gene. International Symposium Iron in Biology and Medicine. Saint-Malo, France', 'author': 'Douabin', 'year': '1997'} / Polymorphisms in the haemochromatosis gene. International Symposium Iron in Biology and Medicine. Saint-Malo, France by Douabin (1997)
10.1136/jmg.34.4.275 / J Med Genet / Global prevalence of putative haemochromatosis mutations. by Merryweather-Clarke (1997)
10.7326/0003-4819-127-2-199707150-00002 / Ann Intern Med / Clinical features of genetic hemochromatosis in women compared with men. by Moirand (1997)

Dates

Type	When
Created	5 years, 10 months ago (Oct. 14, 2019, 4:58 a.m.)
Deposited	5 years, 6 months ago (Feb. 12, 2020, 11:20 a.m.)
Indexed	2 weeks, 1 day ago (Aug. 7, 2025, 5:08 p.m.)
Issued	26 years, 4 months ago (April 15, 1999)
Published	26 years, 4 months ago (April 15, 1999)
Published Print	26 years, 4 months ago (April 15, 1999)

Funders 0

None

BibTeX

@article{Mura_1999, title={HFE Mutations Analysis in 711 Hemochromatosis Probands: Evidence for S65C Implication in Mild Form of Hemochromatosis}, volume={93}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v93.8.2502}, DOI={10.1182/blood.v93.8.2502}, number={8}, journal={Blood}, publisher={American Society of Hematology}, author={Mura, Catherine and Raguenes, Odile and Férec, Claude}, year={1999}, month=apr, pages={2502–2505} }

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