Mutation Analysis in Hereditary Hemochromatosis

Beutler, Ernest; Gelbart, Terri; West, Carol; Lee, Pauline; Adams, Michele; Blackstone, Ryan; Pockros, Paul J.; Kosty, Michael P.; Venditti, Charles P.; Phatak, Pradyumna D.; Seese, Nicole K.; Chorney, Karen; Elshof, Amy E. Ten; Gerhard, Glenn S.; Chorney, Michael J.

doi:10.1006/bcmd.1996.0027

Cited by 391 publications

(228 citation statements)

References 13 publications

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“…These findings are different from those reported for Northern Europe, where more than 90% of the patients are C282Y homozygotes or C282Y and H63D compound heterozygotes (5,(20)(21)(22)(23)(24)(25), but agree with recent data reported for Italy, where approximately one third of the patients with HH showed neither C282Y or H63D mutations, nor any other mutation in the HFE gene by sequence analysis (26)(27)(28). Similarly, none of these mutations were detected in African Americans with HH or in subjects with African iron overload, another hereditary disorder of iron metabolism that is much more heterogeneous than HH (12,13).…”

Section: Discussioncontrasting

confidence: 86%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.

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Section: Discussioncontrasting

confidence: 86%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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“…This is a new MHC class I-like gene, where homozygosity for a single base pair mutation (C282Y), resulting in a cystein to tyrosine substitution at position 282, was found in 83% of HH patients. This finding was promptly confirmed by other groups who described the presence of the C282Y mutation in varying, but always very high, numbers of hemochro-matosis patients in several parts of the world (Barton et al 1997;Beutler et al 1996;Borot et al 1997;Carella et al 1997;Jazwinska et al 1996;Jouanolle et al 1996). A second mutation was also found in the HFE gene (H63D) resulting in a histidine to aspartic acid substitution at position 63.…”

Section: Introductionsupporting

confidence: 58%

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Porto

Alves²,

Rodrigues³

et al. 1998

Immunogenetics

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“…10 This gene encodes an HLA class I-like protein and is mutated in greater than 85% of the patients with HHC of northern European descent. [10][11][12] Genetic testing was not possible in the current cohort. Therefore, this study did not analyze outcome based on HFE genotype.…”

Section: Discussionmentioning

confidence: 92%

Long-term follow-up after liver transplantation in patients with hepatic iron overload

et al. 1999

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Patients with hepatic iron overload who undergo orthotopic liver transplantation (OLT) have a worse 1-year survival than those who undergo transplantation for other indications; the long-term outcome in this population is unknown. The purpose of this study is to report long-term follow-up after OLT in a cohort of patients with hepatic iron overload. Five liver transplant centers in the United States reported follow-up data on 37 patients receiving a first liver transplant who had severe hepatic iron overload in their native livers. KaplanMeier 5-year survival among these patients was compared with survival data from all age-matched liver transplantations reported to the United Network for Organ Sharing (UNOS) over the same time period (1987 to 1993). The 5-year survival rate after OLT was 40% in the hepatic iron overload group compared with an overall survival rate of 62% for all patient groups from the UNOS registry (P ‫؍‬ .0009). Although sepsis was the cause of 53% of all deaths occurring within the first year after OLT, cardiac complications accounted for 50% of the late mortality in patients with hepatic iron overload. In conclusion, longterm survival after OLT is significantly decreased in patients with hepatic iron overload. Infectious and cardiac complications are the most common causes of death in these patients. Further studies are needed to define the relationship between hepatic iron overload and mortality and to examine the effect of iron depletion on outcome after OLT in this patient population.

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Mutation Analysis in Hereditary Hemochromatosis

Cited by 391 publications

References 13 publications

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Long-term follow-up after liver transplantation in patients with hepatic iron overload

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