Hereditary haemochromatosis mutation frequencies in the general population

This study aims to expand our knowledge of the general population frequency of two mutations, C282Y and H63D, identified in the candidate gene for hereditary haemochromatosis, and to determine whether the testing can be performed using routinely obtained cheek-brush (buccal) samples.

Banked buccal lysate samples, randomised and coded for anonymity, from a cohort of couples who underwent prenatal cystic fibrosis screening in Maine.

A multiplex ARMS test was performed on buccal cell lysates to identify the two mutations.

Genotype frequencies found among the 1001 subjects studied (502 women, 499 men) were: seven C282Y homozygotes, 22 C282Y/H63D compound heterozygotes, 97 C282Y heterozygotes, 17 H63D homozygotes, 246 H63D heterozygotes, and 612 individuals with no detectable mutation. The allele frequencies for C282Y and H63D were 0.066 and 0.151, respectively.

Observed genotype frequencies in Maine are consistent with expectations and with consensus data from five smaller studies. Combined mutational analysis data indicate that homozygosity for C282Y (the genotype found in about 85% of subjects with diagnosed hereditary haemochromatosis) occurs in 51 per 10,000 white subjects of northern European heritage; the corresponding total hereditary haemochromatosis prevalence of about 60 per 10,000 is consistent with previous estimates. The study also confirms that H63D would not be useful in general population screening for hereditary haemochromatosis.