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DMXX
08-07-2012, 03:45 PM
23andMe have now added results for a third mutation (S65C) but have omitted specific results if an individual has only one copy of any of the three mutations on the HFE gene implicated in haemochromatosis (C282Y, H63D and now S65C):


http://i46.tinypic.com/10zp7vo.jpg

Therefore, if you had neither the C282Y or H63D mutations before but display results now, you have the S65C mutation.

Some epidemiological information on the prevalence of all three mutations;



• Autosomal recessive.
• Allele frequency of the common HFE mutations varies by ethnicity
• C282Y: Caucasians, 0.09; Hispanics, 0.03; AfricanAmericans, 0.02; Asians, <0.01.
• H63D: Caucasians, 0.25; Hispanic, 0.18; AfricanAmerican, 0.06; Asian, 0.09.
• S65C: Caucasians, 0.015; unknown in other ethnicities.
• About 85 percent of Caucasians with HH are homozygous for C282Y, and 5 percent are compound heterozygous for C282Y/H63D. The S65C mutation accounts for less than 1 percent of HH cases.
• Heterozygotes for HFE gene mutations do not develop clinical symptoms of HH but may have elevated serum iron levels.
• Biochemical and clinical penetrance differ by age and sex. Approximately 80 percent of men and 35 percent of women under 40, as well as 95 percent of men and 80 percent of women over 40, with the C282Y/C282Y genotype will develop iron overload.
• Although biochemical abnormalities are often present in individuals with two HFE mutations, incidence of disease is low and estimated at 5 percent for C282Y homozygotes, 0.5–1.5 percent for C282Y/H63D compound heterozygotes, and rare for H63D homozygotes.
• Approximately 5 percent of individuals with clinical HH are heterozygous for C282Y, suggesting the presence of a second, rare HFE mutation (or mutation in a different iron-related gene).
• Due to the high carrier frequency of HFE mutations in the Caucasian population, the risk for offspring to inherit a highrisk genotype when one parent is known to have HH is 5 percent.


[Link (http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/hemochromatosis_3mutations.pdf)]

Spark
08-08-2012, 01:11 AM
Shoot...I am one of these people. I tested negative for all condition-associated mutations on these SNPs before, now I am testing positive on the new mutation they surveyed. According to 23andme, this was passed on to me through my mother.

DMXX
08-08-2012, 07:01 PM
Shoot...I am one of these people. I tested negative for all condition-associated mutations on these SNPs before, now I am testing positive on the new mutation they surveyed. According to 23andme, this was passed on to me through my mother.

I wouldn't be too concerned Spark. :)

As haemochromatosis itself is an autosomal recessive condition, one would require two pairs of any of the mutations to have it. Otherwise, your ferritin levels will be just fine.

The H63D and S65C are associated with a "milder form of HH [Hereditary Haemochromatosis]" (see here (http://www.biomedcentral.com/1471-2350/8/69/)). Therefore, even if you have a child in the future and your partner carries the S65C mutation as well, that child will have a 25% chance of acquiring both copies and having the (thankfully) milder form.

Mamluk
12-04-2015, 01:52 PM
To supplement the aforementioned epidemiological information, this study by the University of Alabama (http://www.researchgate.net/publication/6733815_Geographic_and_racialethnic_differences_in _HFE_mutation_frequencies_in_the_Hemochromatosis_a nd_Iron_Overload_Screening_(HEIRS)_Study), describes the prevalence and distribution of hemochromatosis in the United States.

This 2013 New England Journal of Medicine study (http://www.nejm.org/doi/full/10.1056/NEJMc1303066)suggests that individuals with hemochromatosis tend to be a few centimeters taller than average.

My father and I are heterozygote for the hemochromatosis mutation, H63D, which appears to be much older than C282Y. It has been suggested that this mutation, which causes increased iron absorption when homozygous for the gene, evolved as a response to famine and survival in harsh conditions. The traditional remedy for such a condition is regular blood-letting.