Objective
Hereditary hemochromatosis (HH) is a common Men
delian disor
der of iron metabolism. Eighty percent of northern Europeans
descendant HH patients carry the same mutation (p.C282Y) in the
HFE gene. Simultaneously, due to a foun
der effect, its frequency varies consi
derably between different populations. In Central-Southern Italy the prevalence of p.C282Y mutation is low and in several patients the disease has different causes. Four additional rarer forms have been
described. Type 3 HH has been reported in about 50 families and no more than 30
TFR2 pathogenic mutations have been globally i
dentified. The aim of this study is to assess the
TFR2 role in non-
HFE HH pathogenesis.
Study design and setting
TFR2 sequence analysis was performed on 45 Italian patients without HFE mutations.
Results
This study revealed TFR2 biallelic pathogenic mutations in 7/45 (15.6%) individuals. Moreover monoallelic TFR2 deleterious defects (18%) or polymorphisms with unclear meaning (36%) were identified. Besides, we recognized 10 novel variants and 9 described changes.
Conclusion
We believe this to be the largest series of type 3 HH patients described so far. Present findings support the hypothesis of a main role of the TFR2 gene in HH pathogenesis in those regions, such as Central-Southern Italy, where the p.C282Y frequency is low.