Objective: Hereditary hemochromatosis (HH) is a common mendelian disorder of iron metabolism. Eighty percent of northern Europeans descendant HH patients carry the same mutation (p.C282Y) in HFE gene. Simultaneously, due to a founder effect, its frequency varies considerably 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 identified. 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 recognised 10 novel variants and 9 described changes. Conclusion: This is supposedly 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.

Objective: Hereditary hemochromatosis (HH) is a common Mendelian disorder 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 founder effect, its frequency varies considerably 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 identified. 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. (C) 2013 Elsevier Inc. All rights reserved.

TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy / Radio, FRANCESCA CLEMENTINA; Silvia, Majore; Binni, Francesco; Michele, Valiante; Bianca Maria, Ricerca; Carmelilia De, Bernardo; Grammatico, Paola. - In: BLOOD CELLS, MOLECULES, & DISEASES. - ISSN 1079-9796. - STAMPA. - 52:2-3(2014), pp. 83-87. [10.1016/j.bcmd.2013.08.003]

TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy

RADIO, FRANCESCA CLEMENTINA;BINNI, FRANCESCO;GRAMMATICO, Paola
2014

Abstract

Objective: Hereditary hemochromatosis (HH) is a common mendelian disorder of iron metabolism. Eighty percent of northern Europeans descendant HH patients carry the same mutation (p.C282Y) in HFE gene. Simultaneously, due to a founder effect, its frequency varies considerably 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 identified. 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 recognised 10 novel variants and 9 described changes. Conclusion: This is supposedly 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.
2014
Objective: Hereditary hemochromatosis (HH) is a common Mendelian disorder 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 founder effect, its frequency varies considerably 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 identified. 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. (C) 2013 Elsevier Inc. All rights reserved.
mediterranean area; tfr2; novel mutations; non-hfe hereditary hemochromatosis.; iron overload; non-hfe hereditary hemochromatosis; hereditary hemochromatosis
01 Pubblicazione su rivista::01a Articolo in rivista
TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy / Radio, FRANCESCA CLEMENTINA; Silvia, Majore; Binni, Francesco; Michele, Valiante; Bianca Maria, Ricerca; Carmelilia De, Bernardo; Grammatico, Paola. - In: BLOOD CELLS, MOLECULES, & DISEASES. - ISSN 1079-9796. - STAMPA. - 52:2-3(2014), pp. 83-87. [10.1016/j.bcmd.2013.08.003]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/543291
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