Haemochromatosis mutations in North-East Scotland

The HFE gene and its mutations C282Y and H63D cause hereditary haemochromat osis (HH). Among 54 affected individuals from North-East Scotland, 91% were homozygous for C282Y and 5.5% were compound heterozygotes for C282Y and H6 3D. The general population allele frequencies were high (8% and 15.7% for C 282Y and H63D respectively). Although it is likely that HH is under diagnos ed, these figures suggest that disease expression is variable, and many of those with the genetic predisposition HH will never develop the clinical co nsequences of iron overload. This has implications for diagnosis and predic tive testing.