PDF下载 ( 2259 KB)
A family with hereditary hemochromatosis carrying HFE gene splice site mutation: a case report
-
摘要:
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。
Abstract: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.
-
Key words:
- hemochromatosis /
- point mutation /
- genes /
- regulator
-
[1]European Association for the Study of the Liver.EASL clinical practice guidelines for HFE hemochromatosis[J].J Hepatol,2010,53(1):3-22. [2]BACON BR,ADAMS PC,KOWDLEY KV,et al.Diagnosis and management of hemochromatosis:2011 practice guideline by the American Association for the Study of Liver Diseases[J].Hepatology,2011,54(1):328-343. [3]BLACHIER M,LELEU H,PECK-RADOSAVLJEVIC M,et al.The burden of liver disease in Europe:a review of available epidemiological data[J].J Hepatol,2013,58(3):593-608. [4]ZOLLER H,HENNINGER B.Pathogenesis,diagnosis and treatment of hemochromatosis[J].Dig Dis,2016,34(4):364-373. [5]KATSAROU MS,LATSI R,PAPASAVVA M,et al.Populationbased analysis of the frequency of HFE gene polymorphisms:correlation with the susceptibility to develop hereditary hemochromatosis[J].Mol Med Rep,2016,14(1):630-636. [6]JIANG J,HUANG JM,QIAN W,et al.Clinical research and preliminarily exploration of genetic basis on a hereditary hemachromatosis pedigree[J].Chin J Hepatol,2010,18(11):842-844.(in Chinese)江军,黄金明,钱伟,等.一个遗传性血色病家系的临床特点及其遗传基础初探[J].中华肝脏病杂志,2010,18(11):842-844. [7]Mc DONALD CJ,WALLACE DF,CRAWFORD DH,et al.Iron storage disease in Asia-Pacific populations:the importance of nonHFE mutations[J].Gastroenterol Hepatol,2013,28(7):1087-1094. [8]WALLACE DF,SUMMERVILLE L,CRAMPTON EM,et al.Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload[J].Hepatology,2009,50(6):1992-2000. [9]PAPANIKOLAOU G,SAMUELS ME,GOLDBERG YP,et al.Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis[J].Nat Genet,2004,36(1):77-82. [10]HUANG FW,RUBIO-ALIAGA I,KUSHNER JP,et al.Identification of a novel mutation(C321X)in HJV[J].Blood,2004,104(7):2176-2177. [11]LI SF,XUE J,ZHANG L,et al.Two middle-age-onset hemochromatosis patients with heterozygous mutations in the hemojuvelin gene in a Chinese family[J].Int J Hematol,2014,99(4):487-492. [12]CAMASCHELLA C,ROETTO A,CALIA,et al.The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22[J].Nat Genet,2000,25(1):14-15. [13]CHEN J,ENNS CA.Hereditary hemochromatosis and transferrin receptor 2[J].Biochim Biophys Acta,2012,1820(3):256-263. [14]OLYNYK JK,TRINDER D,RAMM GA,et al.Hereditary hemochromatosis in the post-HFE era[J].Hepatology,2008,48(3):991-1001. [15]ACTONRT,BARTON JC,SNIVELY BM,et al.Geographic and racial/ethnic differences in HFE mutation frequencies in the Hemochromatosis and Iron Overload Screening(HEIRS)Study[J].Ethn Dis,2006,16(4):815-821. -
本文二维码
计量
- 文章访问数: 2868
- HTML全文浏览量: 51
- PDF下载量: 478
- 被引次数: 0
下载:
