我国人群遗传性血色病基因突变特点分析

Characteristics of gene mutation in Chinese patients with hereditary hemochromatosis

目的分析我国人群遗传性血色病(HH)的基因突变特点。方法选取2013年1月-2015年12月就诊于首都医科大学附属北京友谊医院的9例HH患者,提取基因组DNA,对4种类型HH基因HFE(Ⅰ型)、HJV(ⅡA型)、HAMP(ⅡB型)、TFR2(Ⅲ型)及SLC40A1(Ⅳ型)所有外显子进行PCR扩增和Sanger测序,分析基因突变情况;另选取50例健康人群作为对照组,分析已鉴定的基因突变在健康人群中的表达情况。结果 9例HH患者中,存在Ⅰ型HFE基因H63D突变2例、ⅡA型HJV基因E3D突变1例、Ⅲ型TFR2基因I238M突变2例,Ⅳ型SLC40A1基因IVS 3+10 del GTT剪切突变1例,未检出欧美人群常见的Ⅰ型HFE C282Y突变。5例患者未检测出任何错义或剪切突变。此外,在一个遗传家系中发现HH患者同时存在HFE H63D、HJV E3D及TFR2I238M突变,但携带其中2个突变的健康兄妹没有出现HH表型。结论 HH基因突变在不同种族患者中存在较大的差异,我国可能以非HFE型HH为主,推测可能存在与目前已知基因不同的HH相关基因,需进一步研究证实。

Objective To investigate the characteristics of gene mutation in Chinese patients with hereditary hemochromatosis（ HH）.Methods A total of 9 patients with HH who visited Beijing Friendship Hospital,Capital Medical University from January 2013 to December2015 were enrolled. The genomic DNA was extracted,and PCR amplification and Sanger sequencing were performed for all the exons of four genotypes of HH,i. e.,HFE（ type Ⅰ）,HJV（ type ⅡA）,HAMP（ type ⅡB）,TFR2（ type Ⅲ）,and SLC40A1（ type Ⅳ） to analyze gene mutations. A total of 50 healthy subjects were enrolled as control group to analyze the prevalence of identified gene mutations in a healthy population. Results Of all patients,2 had H63 D mutation of HFE gene in type Ⅰ HH,1 had E3 D mutation of HJV gene in typeⅡA HH,2 had I238 M mutation of TFR2 gene in type Ⅲ HH,and 1 had IVS 3 ＋ 10 del GTT splice mutation of SLC40A1 gene in type ⅣHH. No patients had C282 Y mutation of HFE gene in type Ⅰ HH which was commonly seen in European and American populations. Five patients had no missense mutation or splice mutation. In addition,it was found in a family that a HH patient had E3 D mutation of HJV gene,H63 D mutation of HFE gene,and I238 M mutation of TFR2 gene,but the healthy brother and sister carrying two of these mutations did not had the phenotype of HH. Conclusion HH gene mutations vary significantly across patients of different races,and non- HFE- HH is dominant in the Chinese population. There may be HH genes which are different from known genes,and further investigation is needed.