Barton J C, West C, Lee P L, Beutler E
Southern Iron Disorders Center, Birmingham, AL, USA.
Clin Genet. 2004 Sep;66(3):214-6. doi: 10.1111/j.1399-0004.2004.00285.x.
A 62-year-old white man with a hemochromatosis phenotype was found to be heterozygous for the C282Y mutation of the HFE gene. The H63D and S65C mutations of HFE were not present. As most C282Y heterozygotes do not develop a hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed frameshift mutation was identified in exon 2 (c.del277; G93fs) that resulted in a premature stop-codon. There were no coding region mutations of the ferroportin gene (FPN1). We performed human leukocyte antigen (HLA) typing of the patient and his brother who was heterozygous for the C282Y HFE mutation unassociated with a hemochromatosis phenotype. They shared only C282Y and the HLA haplotype A03, B14; hence, the c.del277 mutation was linked to the HLA haplotype A02, B44 and therefore not on the same chromosome as the C282Y mutation. Thus, the present patient's only intact HFE protein is C282Y, and this may explain his hemochromatosis phenotype.
一名表现出遗传性血色素沉着症表型的62岁白人男性被发现HFE基因的C282Y突变呈杂合状态。未检测到HFE基因的H63D和S65C突变。由于大多数C282Y杂合子不会出现遗传性血色素沉着症表型，因此对该患者的HFE基因编码区进行了测序，并在外显子2中鉴定出一种先前未描述的移码突变（c.del277；G93fs），该突变导致了提前终止密码子。铁转运蛋白基因（FPN1）的编码区未发现突变。我们对该患者及其兄弟进行了人类白细胞抗原（HLA）分型，其兄弟为C282Y HFE突变杂合子，但未表现出遗传性血色素沉着症表型。他们仅共享C282Y和HLA单倍型A03、B14；因此，c.del277突变与HLA单倍型A02、B44连锁，因此与C282Y突变不在同一条染色体上。因此，该患者唯一完整的HFE蛋白是C282Y，这可能解释了他的遗传性血色素沉着症表型。
