Biasiotto Giorgio, Roetto Antonella, Daraio Filomena, Polotti Anna, Gerardi Gian Mario, Girelli Domenico, Cremonesi Laura, Arosio Paolo, Camaschella Clara
Dipartimento Materno Infantile e Tecnologie Biomediche, Università di Brescia, A.O. Spedali Civili, Brescia, Italy.
Blood Cells Mol Dis. 2004 Nov-Dec;33(3):338-43. doi: 10.1016/j.bcmd.2004.08.002.
HFE-hemochromatosis is the most common form of hereditary hemochromatosis. The disorder is associated with the homozygous C282Y mutation and has variable phenotype, being modulated by environmental and genetic factors. Candidate modifier genes are hemojuvelin and hepcidin, which are responsible for juvenile hemochromatosis. We used DHPLC to scan mutations in these genes in a cohort of unrelated patients with C282Y mutation. They consisted of 136 C282Y homozygous, 43 heterozygous, and 42 C282Y/H63D compound heterozygous, plus 62 controls subjects. Mutations and polymorphisms were found in 16 patients and 4 controls. Abnormally high indices of iron status were found in subjects C282Y/H63D heterozygous for the N196K hemojuvelin mutation and the -72C > T hepcidin substitution. The already described G71D mutation of hepcidin did not induce evident modification of the C282Y/H63D phenotype. The data show that heterozygous mutations of the hemojuvelin gene contribute like those of hepcidin to the phenotypic heterogeneity of hemochromatosis. However, they are rare and explain only a minor portion of the variable penetrance of the disorder.
HFE 遗传性血色素沉着症是遗传性血色素沉着症最常见的形式。该病症与纯合子 C282Y 突变相关，具有可变的表型，受环境和遗传因素调节。候选修饰基因是血色素沉着蛋白和铁调素，它们与青少年血色素沉着症有关。我们使用变性高效液相色谱法（DHPLC）对一组携带 C282Y 突变的无关患者的这些基因中的突变进行扫描。他们包括 136 名 C282Y 纯合子、43 名杂合子和 42 名 C282Y/H63D 复合杂合子，外加 62 名对照受试者。在 16 名患者和 4 名对照中发现了突变和多态性。在 N196K 血色素沉着蛋白突变和 -72C>T 铁调素替代的 C282Y/H63D 杂合子受试者中发现铁状态指标异常高。已描述的铁调素 G71D 突变并未引起 C282Y/H63D 表型的明显改变。数据表明，血色素沉着蛋白基因的杂合子突变与铁调素基因的杂合子突变一样，对血色素沉着症的表型异质性有影响。然而，它们很少见，仅解释了该病症可变外显率的一小部分。
