NCBI
PubMed
A service of the
U.S. National Library of Medicine
and the
National Institutes of Health
My NCBI
[Sign In]
[Register]
All Databases
PubMed
Nucleotide
Protein
Genome
Structure
OMIM
PMC
Journals
Books
Search
Database name
PubMed
Protein
Nucleotide
GSS
EST
Structure
Genome
Books
CancerChromosomes
Conserved Domains
dbGaP
3D Domains
Gene
Genome Project
GENSAT
GEO Profiles
GEO DataSets
HomoloGene
Journals
MeSH
NCBI Web Site
NLM Catalog
OMIA
OMIM
PMC
PopSet
Probe
Protein Clusters
PubChem BioAssay
PubChem Compound
PubChem Substance
SNP
Taxonomy
ToolKit
UniGene
UniSTS
for
Search term
Go
Clear
Advanced Search (beta)
Limits
Preview/Index
History
Clipboard
Details
Display
Summary
Brief
Abstract
AbstractPlus
Citation
MEDLINE
XML
UI List
LinkOut
ASN.1
Related Articles
Cited in Books
CancerChrom Links
Domain Links
3D Domain Links
dbGaP Links
GEO DataSet Links
Gene Links
Gene (OMIM) Links
Gene (GeneRIF) Links
Genome Links
Project Links
GENSAT Links
GEO Profile Links
HomoloGene Links
Nucleotide Links
Nucleotide (RefSeq) Links
Nucleotide (Weighted) Links
EST Links
EST (RefSeq) Links
GSS Links
GSS (RefSeq) Links
OMIA Links
OMIM (calculated) Links
OMIM (cited) Links
BioAssay Links
Compound Links
Compound (MeSH Keyword)
Compound (Publisher) Links
Substance Links
Substance (MeSH Keyword)
Substance (Publisher) Links
PMC Links
Cited in PMC
PopSet Links
Probe Links
Protein Links
Protein (RefSeq) Links
Protein (Weighted) Links
Protein Cluster Links
Cited Articles
SNP Links
SNP (Cited)
Structure Links
Taxonomy via GenBank
UniGene Links
UniSTS Links
Show
5
10
20
50
100
200
500
Sort By
Pub Date
First Author
Last Author
Journal
Title
Send to
Text
File
Printer
Clipboard
Collections
E-mail
Order
All: 1
Review: 0
Click to change filter selection through MyNCBI.
1:
Lancet.
2002 Jan 19;359(9302):211-8.
Related Articles
,
Links
Comment in:
Hepatology 2002 Aug;36(2):500-3.
Lancet. 2002 Aug 3;360(9330):411-2; author reply 413-4.
Lancet. 2002 Aug 3;360(9330):412-3; author reply 413-4.
Lancet. 2002 Aug 3;360(9330):412; discussion 413-4.
Lancet. 2005 Jul 23-29;366(9482):269-71.
Penetrance of 845G--> A (C282Y) HFE hereditary haemochromatosis mutation in the USA.
Beutler E
,
Felitti VJ
,
Koziol JA
,
Ho NJ
,
Gelbart T
.
Scripps Research Institute, Department of Molecular and Experimental Medicine, Divisions of Hematology, La Jolla, CA 92037, USA. beutler@scripps.edu
BACKGROUND: There has been much interest in screening populations for disease-associated mutations. A favoured candidate has been the HFE gene, mutations of which are the most common cause of haemochromatosis in the European population. About five people in 1000 are homozygotes for the 845G-->A mutation, but little is known of how many have mutation-caused clinical manifestations. METHODS: We screened 41038 individuals attending a health appraisal clinic in the USA for the 845G--> A and 187C-->G HFE mutations, and analysed laboratory data and data on signs and symptoms of haemochromatosis as elicited by questionnaire. FINDINGS: The most common symptoms of haemochromatosis, including poor general health, diabetes, arthropathies, arrhythmias, impotence, and skin pigmentation were no more prevalent among the 152 identified homozygotes than among the controls. The age distribution of homozygotes and compound heterozygotes did not differ significantly from that of controls: there was no measurable loss of such individuals from the population during ageing. However, there was a significantly increased prevalence of a history of hepatitis or "liver trouble" among homozygotes and in the proportion of homozygotes with increased concentrations of serum aspartate aminotransferase and collagen IV; these changes were not related to iron burden or to age. Only one of the 152 homozygotes had signs and symptoms that would suggest a diagnosis of haemochromatosis. INTERPRETATION: The normal age distribution of people with the haemochromatosis genotype, and the lack of symptoms in patients of all ages, indicate that the penetrance of hereditary haemochromatosis is much lower than generally thought. The clinical penetrance of a disorder is an essential consideration in screening for genetic disease; disorders with low penetrance are more expensive candidates for screening than disorders with high penetrance. Our best estimate is that less than 1% of homozygotes develop frank clinical haemochromatosis.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 11812557 [PubMed - indexed for MEDLINE]
Display
Summary
Brief
Abstract
AbstractPlus
Citation
MEDLINE
XML
UI List
LinkOut
ASN.1
Related Articles
Cited in Books
CancerChrom Links
Domain Links
3D Domain Links
dbGaP Links
GEO DataSet Links
Gene Links
Gene (OMIM) Links
Gene (GeneRIF) Links
Genome Links
Project Links
GENSAT Links
GEO Profile Links
HomoloGene Links
Nucleotide Links
Nucleotide (RefSeq) Links
Nucleotide (Weighted) Links
EST Links
EST (RefSeq) Links
GSS Links
GSS (RefSeq) Links
OMIA Links
OMIM (calculated) Links
OMIM (cited) Links
BioAssay Links
Compound Links
Compound (MeSH Keyword)
Compound (Publisher) Links
Substance Links
Substance (MeSH Keyword)
Substance (Publisher) Links
PMC Links
Cited in PMC
PopSet Links
Probe Links
Protein Links
Protein (RefSeq) Links
Protein (Weighted) Links
Protein Cluster Links
Cited Articles
SNP Links
SNP (Cited)
Structure Links
Taxonomy via GenBank
UniGene Links
UniSTS Links
Show
5
10
20
50
100
200
500
Sort By
Pub Date
First Author
Last Author
Journal
Title
Send to
Text
File
Printer
Clipboard
Collections
E-mail
Order
About Entrez
Text Version
Entrez PubMed
Overview
Help
|
FAQ
Tutorials
New/Noteworthy
E-Utilities
PubMed Services
Journals Database
MeSH Database
Single Citation Matcher
Batch Citation Matcher
Clinical Queries
Special Queries
LinkOut
My NCBI
Related Resources
Order Documents
NLM Mobile
NLM Catalog
NLM Gateway
TOXNET
Consumer Health
Clinical Alerts
ClinicalTrials.gov
PubMed Central
Write to the Help Desk
NCBI
|
NLM
|
NIH
Department of Health & Human Services
Privacy Statement
|
Freedom of Information Act
|
Disclaimer