Estimated analytic validity of HFE C282Y mutation testing in population screening: the potential value of confirmatory testing.
OBJECTIVE
The purpose of this study was to estimate analytic sensitivity and specificity of HFE testing for C282Y homozygosity in the hypothetical setting of population screening for hemochromatosis.


METHODS
We analyzed published results of the Molecular Genetics Survey performed by the American College of Medical Genetics/College of American Pathologists between 1998 and 2002, taking into account its educational nature.


RESULTS
Analytic sensitivity for C282Y homozygosity is 98.4% (95% CI 95.9%-99.5%). The analytic specificity is 99.8% (99.4%-99.9%). At a frequency of 40 per 10,000 for the homozygous genotype, the analytic positive predictive value is 66%.


CONCLUSIONS
HFE testing for C282Y homozygosity is highly reliable. Homozygosity is uncommon in population screening, however, and confirmatory testing should be considered.
Palomaki
Glenn E
GE
Foundation for Blood Research, Scarborough, Maine 04070-0190, USA.
Haddow
James E
JE
Bradley
Linda A
LA
Richards
C Sue
CS
Stenzel
Timothy T
TT
Grody
Wayne W
WW
D005820:Genetic Testing; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012680:Sensitivity and Specificity
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins