目的：探讨1例新型的遗传性血色病（HH）患者家系 HFE 基因突变形式。方法对确诊的1例 HH 患者分析其与5位相关亲属的血色病基因，提取血液基因组 DNA，采用 PCR 扩增相关基因 HFE、HJV、HAMP、转铁蛋白受体（TfR）2、SLC40A1的外显子、内含子剪切序列，琼脂糖凝胶电泳、纯化后，双向直接测序检测突变位点。结果先证者肝功能异常，血清铁（SI）、总铁结合力（TIBC）、铁蛋白（SF）、转铁蛋白饱和度（TS）均升高，HFE 基因外显子 EXON2的区间序列2号内含子第4个碱基出现 T→C 纯合突变（IVs 2＋4T→C，C ／C 纯合，splicing，异常），HJV、HAMP、TfR2、SLC40A1未见异常，患者儿子出现与其相同纯合突变，3位亲属存在杂合突变，1位亲属无异常突变。结论基因检测在血色病诊断中起着重要作用，HFE 基因 IVs 2＋4T→C 突变可能是新型的中国HH 的致病遗传基因突变类型。%Objective To investigate a new type of HFE gene mutation in a family with hereditary hemochromatosis (HH).Methods The analysis of HFE gene was performed for one patient with a confirmed diagnosis of HH and five relatives.Blood genomic DNA was extracted and PCR multiplication was performed for the exon and intron splice sequences of related HFE,HJV,HAMP,transferrin receptor 2 (TfR2),and SLC40A1 genes.After agarose gel electrophoresis and purification,bi -directional direct sequencing was performed to detect mutation sites.Results The proband had abnormal liver function and increases in serum iron,total iron binding capacity,serum ferritin, and transferrin saturation,as well as T→C homozygous mutation in the fourth base of intron 2 in the intervening sequence of the exon EXON2 of HFE gene (IVs 2 +4T→C,C /C homozygous,splicing,abnormal).There were no abnormalities in HJV,HAMP,TfR2,and SLC40A1 genes.The proband′s son had the same homozygous mutation,three relatives had heterozygous mutations,and one relative had no abnormal mutations.Conclusion Gene detection plays an important role in the diagnosis of hemochromatosis,and IVs 2 +4T→C mutation may be a new pathogenic mutation for HH in China.
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