Beutler E, Griffin M J, Gelbart T, West C
The Scripps Research Institute, Department of Molecular and Experimental Medicine, Division of Hematology, La Jolla, CA 92037, USA.
Clin Genet. 2002 Jan;61(1):40-2. doi: 10.1034/j.1399-0004.2002.610108.x.
A patient with clinically manifest hereditary hemochromatosis was found to be heterozygous for the c.845 A-->G (C282Y) mutation. As simple heterozygotes for this mutation do not develop the hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed nonsense mutation was identified at c.211 C-->T (R74X). The patient's brother who also had the hemochromatosis phenotype shared his HFE genotype. To determine how common such mutations might be, the coding and 5' region of the HFE genes of 11 subjects who had been found in a large population survey to be heterozygous for the C282Y mutation and had elevated ferritin levels were sequenced. No mutations were found. Sequencing of the HFE gene also revealed two polymorphisms that had not previously been noted, -467 C-->G and -970 T-->G. Neither of these mutations appear to cause an abnormality in iron metabolism.
一名临床表现为遗传性血色素沉着症的患者被发现为c.845 A→G（C282Y）突变的杂合子。由于该突变的单纯杂合子不会出现血色素沉着症表型，因此对该患者HFE基因的编码区进行了测序，并在c.211 C→T（R74X）处发现了一个先前未描述的无义突变。该患者同样患有血色素沉着症表型的兄弟具有相同的HFE基因型。为了确定此类突变的常见程度，对在一项大规模人群调查中发现为C282Y突变杂合子且铁蛋白水平升高的11名受试者的HFE基因编码区和5'区域进行了测序。未发现突变。HFE基因测序还揭示了两个先前未被注意到的多态性，即-467 C→G和-970 T→G。这两种突变似乎均未导致铁代谢异常。
