From the Research
Significance of Being Heterozygous for the C282Y Mutation
The significance of being heterozygous for the C282Y mutation in Hereditary Hemochromatosis (HH) can be understood through various studies.
- Heterozygosity for the C282Y mutation does not typically lead to severe iron overload by itself, but when combined with other genetic mutations, such as beta-thalassemia or the H63D mutation, it may increase the risk of iron overload 1, 2.
- Studies have shown that C282Y heterozygotes have a lower risk of developing clinical evidence of iron overload compared to C282Y homozygotes, with an estimated 40-70% of C282Y homozygotes developing clinical evidence of iron overload 3.
- Informing C282Y heterozygotes of their genotype does not appear to increase anxiety or reduce health perception, and may lead to cascade testing in a minority of families 4.
- The clinical significance of the C282Y mutation in combination with other mutations, such as the S65C mutation, is still being studied, but it appears that compound heterozygotes may have a higher risk of iron overload or genetic hemochromatosis than single heterozygotes for the C282Y mutation 5, 2.
Key Findings
- C282Y heterozygosity is relatively common in European populations, with a frequency of 9.2% 3.
- The penetrance of the C282Y mutation is not well understood, but it is estimated that 40-70% of C282Y homozygotes will develop clinical evidence of iron overload 3.
- Compound heterozygotes for the C282Y and H63D mutations may have a higher risk of iron overload or genetic hemochromatosis than single heterozygotes for the C282Y mutation 2.