The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epid...The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epidemiological and molecular approaches, the authors studied： （a） the frequency of the HH main mutations; （b） the association between mutations and HH cases. The majority of patients with HH are homozygous for the C282Y mutation of the HFE gene. A second mutation （H63D） is more widely distributed and its connection with HH isn＇t clear, but a low penetrance is attributed to this variant. The population-based study consists of three steps： （1） determination of iron biochemical parameters, （2） genetic test, and （3） sequencing of HFE gene and bioinformatics studies. A case report is presented in a 41-year-old male （genotype： H63D/wt） with biochemical and clinical evidences of HH, in absence of secondary iron overload factors. In the cohort of studied patients （150M：62F）, there are 18 homozygous patients; H63D/H63D genotype is found in 11 cases. In the heterozygous group, H63D/wt is the predominant genotype （61/68 subjects）. All the H63D/wt residents in the same village （Mont.） show altered biochemical parameter levels. In our case study, a substitution localized into the HFE promoter （nt225A 〉 C） is found. Results show that the H63D genotype is responsible for most cases of HH. The peculiar clinical manifestation found in Mont. suggests a founder effect. In our case, the iron overload is related to a presence of an undetected mutation, critical for the transcriptional regulation of the HFE gene.展开更多
文摘The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epidemiological and molecular approaches, the authors studied： （a） the frequency of the HH main mutations; （b） the association between mutations and HH cases. The majority of patients with HH are homozygous for the C282Y mutation of the HFE gene. A second mutation （H63D） is more widely distributed and its connection with HH isn＇t clear, but a low penetrance is attributed to this variant. The population-based study consists of three steps： （1） determination of iron biochemical parameters, （2） genetic test, and （3） sequencing of HFE gene and bioinformatics studies. A case report is presented in a 41-year-old male （genotype： H63D/wt） with biochemical and clinical evidences of HH, in absence of secondary iron overload factors. In the cohort of studied patients （150M：62F）, there are 18 homozygous patients; H63D/H63D genotype is found in 11 cases. In the heterozygous group, H63D/wt is the predominant genotype （61/68 subjects）. All the H63D/wt residents in the same village （Mont.） show altered biochemical parameter levels. In our case study, a substitution localized into the HFE promoter （nt225A 〉 C） is found. Results show that the H63D genotype is responsible for most cases of HH. The peculiar clinical manifestation found in Mont. suggests a founder effect. In our case, the iron overload is related to a presence of an undetected mutation, critical for the transcriptional regulation of the HFE gene.
