A pilot C282Y hemochromatosis screening in Italian newborns by TaqMan (TM)technology

Hereditary hemochromatosis (HH) is a disorder of iron metabolism that leads to iron overload in middle age and can be caused by homozygosity for the C 282Y mutation in the HFE gene. Preliminary studies have estimated the frequ ency of this mutation at 0.5-1% in Italy, but this has not been verified on a large sample. We analyzed 1,331 Italian newborns for the C282Y mutation in the HFE gene using dried blood spots (DBS) from the Neonatal Screening C enter in Turin, Italy. The mutation was assessed using a semi-automatable 5 '-nuclease assay (TaqMan(TM) technology), We detected 55 heterozygotes and no homozygotes in our sampling, resulting in an overall frequency of 2.1% /- 0.6 for the C282Y allele, Differences in allele frequency were observed, and ranged from 2.7% +/- 1.3 in samples from Northern Italy, to 1.7% +/- 0 .9 in samples from Central-Southern Italy, The low frequency of the at-risk genotype for iron overload suggests that genetic screening for HFE in Ital y would not be cost effective. The present study, in addition to defining C 282Y frequency, documents detection of the major HFE mutation on routine DB S samples from neonatal screening programs using a semi-automatable, rapid, reliable, and relatively inexpensive approach.