Hereditary hemochromatosis (HH; OMIM# 235200) testing identifies mutations in the HFE gene. HFE mutations exhibit incomplete penetrance; therefore, the HFE genotype cannot be used as the sole diagnostic criterion for disease. The majority (approximately 80 " “90%) of HH patients are homozygous for the C282Y mutation. Less than 2% of all C282Y/H63D compound heterozygotes will develop HH. Other reported genotypes associated with a clinical diagnosis of HH include compound heterozygosity for C282Y/S65C and homozygosity for H63D.
Normal values: negative or no mutations are found.
Use
Confirmatory diagnostic testing
Predictive testing for at-risk relatives
Carrier testing (for the identification of heterozygotes)
Prenatal diagnosis (rarely performed)
Two groups of tests are available:
Targeted mutation panels test for only two: p.C282Y (c.845G>A) and p.H63D (c.187C>G), or three mutations including p.S65C (c.193A>T)
HFE gene sequence analysis: analysis of the entire coding region " ”testing to identify rare mutant alleles
Limitations
The results of a genetic test may be affected by DNA rearrangements, blood transfusion, bone marrow transplantation, or rare sequence variations.