Phatak Pradyumna D, Ryan Daniel H, Cappuccio Joseph, Oakes David, Braggins Caroline, Provenzano Kim, Eberly Shirley, Sham Ronald L
Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, USA.
Blood Cells Mol Dis. 2002 Jul-Aug;29(1):41-7. doi: 10.1006/bcmd.2002.0536.
Two HFE gene mutations, C282Y and H63D, underlie the vast majority of cases of hereditary hemochromatosis. We performed a cross-sectional primary care-based study to determine the allele frequency of the C282Y and H63D mutations and the penetrance of each of the affected genotypes defined by their presence. Patients had previously undergone transferrin saturation (TS) testing. A total of 4865 unselected frozen serum samples were analyzed to determine serum ferritin (SF) levels. Genomic DNA isolated from these samples was analyzed for the C282Y and H63D HFE mutations. Homozygotes for each mutation and compound heterozygotes were evaluated to determine clinical penetrance. The allele frequency of C282Y was 0.0507 among Caucasian and 0.0067 among African Americans; that of H63D was 0.1512 and 0.0263, respectively. TS was > or =55% in 83% of individuals with C282Y/C282Y, 14.5% of C282Y/H63D, and 5% of H63D/H63D; SF was > or =300 microG/L in 42, 9, and 5% of these genotypes, respectively. None of the 12 C282Y homozygotes had cardiac dysfunction or hepatic cirrhosis. Only 9/129 (7%) individuals with the genotypes C282Y/H63D or H63D/H63D had a SF > or =300 microG/L; many had explanations other than iron overload that accounted for this increase. Thus, the prevalence of the common HFE mutations is the same in our population as previously described. TS screening would detect most C282Y homozygotes but not the other two genotypes. The penetrance of C282Y/C282Y is significant. The biochemical penetrance of H63D/H63D and C282Y/H63D is modest and the clinical penetrance is low.
两种HFE基因突变，即C282Y和H63D，是绝大多数遗传性血色素沉着症病例的基础。我们开展了一项基于初级保健的横断面研究，以确定C282Y和H63D突变的等位基因频率，以及由其存在所定义的每种受影响基因型的外显率。患者此前已接受转铁蛋白饱和度（TS）检测。共分析了4865份未经筛选的冷冻血清样本，以确定血清铁蛋白（SF）水平。对从这些样本中分离出的基因组DNA进行分析，以检测C282Y和H63D HFE突变。对每种突变的纯合子和复合杂合子进行评估，以确定临床外显率。C282Y的等位基因频率在白种人中为0.0507，在非裔美国人中为0.0067；H63D的等位基因频率分别为0.1512和0.0263。在C282Y/C282Y个体中，83%的人TS≥55%，C282Y/H63D个体中为14.5%，H63D/H63D个体中为5%；在这些基因型中，SF≥300μg/L的比例分别为42%、9%和5%。12名C282Y纯合子均无心脏功能障碍或肝硬化。在C282Y/H63D或H63D/H63D基因型的个体中，只有9/129（7%）的人SF≥300μg/L；许多人除铁过载外还有其他原因导致这种升高。因此，常见HFE突变在我们人群中的患病率与先前描述的相同。TS筛查可检测出大多数C282Y纯合子，但无法检测出其他两种基因型。C282Y/C282Y的外显率显著。H63D/H63D和C282Y/H63D的生化外显率适中，临床外显率较低。
