Cimburová M, Půtová I, Provazníková H, Pintérová D, Horák J
Center of Biomedical Sciences, Division of Cell and Molecular Biology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
Folia Biol (Praha). 2005;51(6):172-6.
HFE-linked hereditary haemochromatosis is a common autosomal recessive disease among Caucasians. The primary pathogenetic mechanism is excessive absorption of iron, which is deposited in various organs with their subsequent damage. In 1996 the gene responsible for haemochromatosis was detected--the HFE gene and its major mutation C282Y. The discovery of further mutations followed. Two sites of point mutations in the HFE gene, C282Y and H63D, are associated with more than 80% of haemochromatosis cases. Another mutation-- S65C--was detected on 8% of chromosomes of haemochromatosis patients, which were negative for mutations C282Y or H63D. The objective of this study was to identify the allele frequency of S65C and other HFE mutations in the Czech population. DNA extracted from 481 randomly selected newborn screening cards (Guthrie cards) from all over the country was analysed by PCR-RFLP. No (0%) sample was identified as homozygous for S65C or C282Y mutation and 8 (1.67%) were homozygous for H63D mutation. Twelve (2.49%) samples were S65C heterozygous, 33 (6.86%) samples were C282Y heterozygous, and 128 (26.61%) were H63D heterozygous. Of these, 11 (2.29%) carried one copy of each mutation, i.e. were compound heterozygous. Two samples were S65C/H63D compound heterozygous and nine were C282Y/H63D compound heterozygous. Allele frequencies for S65C, C282Y, and H63D were 1.25% (95% CI, +/- 0.70), 3.43% (95% CI, +/- 1.15), and 14.97% (95% CI, +/- 2.25), respectively. The observed genotype frequency for S65C, C282Y, and H63D mutations in the Czech Republic agrees with those reported for other Central European populations.
与HFE相关的遗传性血色素沉着症是白种人中常见的常染色体隐性疾病。主要发病机制是铁吸收过多，铁沉积在各个器官并随后造成损害。1996年发现了导致血色素沉着症的基因——HFE基因及其主要突变C282Y。随后又发现了其他突变。HFE基因中的两个点突变位点C282Y和H63D与80%以上的血色素沉着症病例相关。在血色素沉着症患者8%的染色体上检测到另一种突变——S65C，这些染色体的C282Y或H63D突变呈阴性。本研究的目的是确定捷克人群中S65C和其他HFE突变的等位基因频率。通过PCR-RFLP分析从全国随机抽取的481张新生儿筛查卡片（格思里卡片）中提取的DNA。没有（0%）样本被鉴定为S65C或C282Y突变纯合子，8个（1.67%）样本为H63D突变纯合子。12个（2.49%）样本为S65C杂合子，33个（6.86%）样本为C282Y杂合子，128个（26.61%）样本为H63D杂合子。其中，11个（2.29%）携带每种突变的一个拷贝，即复合杂合子。两个样本为S65C/H63D复合杂合子，九个样本为C282Y/H63D复合杂合子。S65C、C282Y和H63D的等位基因频率分别为1.25%（95%CI，±0.70）、3.43%（95%CI，±1.15）和14.97%（95%CI，±2.25）。捷克共和国观察到的S65C、C282Y和H63D突变的基因型频率与其他中欧人群报告的频率一致。
