de Diego Carles, Murga Maria José, Martínez-Castro Pedro
Department of Genetics, Hospital Virgen de la Salud, Toledo, Spain.
Genet Test. 2004 Fall;8(3):263-7. doi: 10.1089/gte.2004.8.263.
Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by a defective iron absorption. C282Y is the most frequent HFE gene mutation causing HH in Northern European populations and their descendants. However, two other mutations, H63D and S65C, have been described as pathogenic changes. In this study, we have tried to evaluate the frequency of these three mutations in our community. Eighty-three patients with clinical and/or biochemical features of hemochromatosis and 150 controls were screened for H63D, S65C, and C282Y mutations using a PCR-restriction fragment length polymorphism (RFLP)-based strategy. In contrast to previous studies, 7% of the patients were homozygous for C282Y mutation. The remaining patients were 20% H63D homozygous, 10% H63D/C282Y compound heterozygous, 1% H63D/S65C compound heterozygous, 22% H63D heterozygous, 2% C282Y heterozygous, 2% S65C heterozygous, and 36% of patients lacked any of the three mutations studied, despite the fact that they showed clinical/biochemical features of hemochromatosis. We observed a high frequency of the H63D mutation in both the control group and patients, whereas the main genotypes implicated in HH in our series were H63D homozygous and H63D/C282Y compound heterozygous. We propose that the H63D mutation be analyzed in HH patients from our geographic area. Moreover, further studies are needed to elucidate the role of this mutation in the development of HH and the genetic, environmental or other factors that affect the genotype-phenotype correlation between H63D and hemochromatosis.
遗传性血色素沉着症（HH）是一种由铁吸收缺陷引起的常染色体隐性疾病。C282Y是北欧人群及其后裔中导致HH的最常见HFE基因突变。然而，另外两种突变H63D和S65C也被描述为致病性改变。在本研究中，我们试图评估这三种突变在我们社区中的发生频率。采用基于聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的方法，对83例具有血色素沉着症临床和/或生化特征的患者以及150名对照者进行了H63D、S65C和C282Y突变筛查。与先前的研究不同，7%的患者为C282Y突变纯合子。其余患者中，20%为H63D纯合子，10%为H63D/C282Y复合杂合子，1%为H63D/S65C复合杂合子，22%为H63D杂合子，2%为C282Y杂合子，2%为S65C杂合子，36%的患者未检测到所研究的三种突变中的任何一种，尽管他们表现出血色素沉着症的临床/生化特征。我们在对照组和患者中均观察到H63D突变的高频率，而在我们的研究系列中，与HH相关的主要基因型为H63D纯合子和H63D/C282Y复合杂合子。我们建议对来自我们地理区域的HH患者进行H63D突变分析。此外，还需要进一步研究以阐明该突变在HH发生发展中的作用，以及影响H63D与血色素沉着症之间基因型-表型相关性的遗传、环境或其他因素。
