探讨Ⅳ型遗传性血色病肝脏hepcidin mRNA表达及意义

To investigate the significance of the expression of hepcidin mRNA in liver tissues of hereditary hemochromatosis type Ⅳ

目的探讨Ⅳ型遗传性血色病肝脏hepcidin mRNA表达及临床意义。方法对一例遗传性血色病先证者的家系进行遗传学问询,病史采集,体格检查,实验室检查,MRI检查及肝脏组织病理学检查,运用实时荧光定量PCR法检测肝脏hepcidin mRNA表达,并进行遗传性血色病发病相关基因的基因筛查。结果该家系15人有7例经MRI证实存在不同程度实质脏器铁沉积,3例接受肝活检者中的2例肝脏组织普鲁士蓝染色证实铁沉积,实时荧光定量PCR法检测显示肝脏hepcidin mRNA表达上调,外周静脉血基因筛查发现2q32的SLC40A1六号外显子有一处碱基发生点突变,即T173C。结论1.本家系罹患Ⅳ型遗传性血色病,遗传学特征为常染色体显性遗传,SLC40A1六号外显子有一处点突变,但该突变与国际上先前报道的突变位点并不相符,说明该基因突变可能是新的突变类型;2.本家系肝脏hepcidin mRNA表达上调,提示血清hepcidin水平升高,说明可能存在hepcidin抵抗现象,使机体对hepcidin负性调节低反应,从而导致铁代谢紊乱出现铁沉积并出现脏器功能损害。

Objective To investigate the expression of hepcidin mRNA in liver tissues of hereditary hemochromatosis type Ⅳ and explore its clinical significance and possible pathogenesis. Methods The family tree of one case of the proband had been studied by inquiring genetically, history collection, physical examination, lab examination （ such as the blood routine, liver of function, serum iron, ferritin test and fasting blood - glucose） as well as the MRI check of the material organs, examination of hepatic pathology and staining by Prussian blue, the expression of hepcidin mRNA was detected in liver tissue by qRT- PCR, and also the gene related to mutation genes of hemochromatosis of the peripheral venous blood was screened. Results 7 cases of 15 family tree members had been checked as that there is visceral organs iron deposit differently, 2 cases of 3 patients been having liver tissue biopsy had been detected iron deposit in liver tissue by staining with Prussian blue. The expression of liver hepcidin mRNA of the 3 patients indicated moving - up by qRT - PCR. A point mu- tation on one base of the sixth extron of SLC40A1 of 2q32 had been detected by gene screening of the peripheral venous blood, i.e. the base of T173C. Conclusions 1. The family tree members are suffering the hereditary hemochromatosis type Ⅳ, and the hereditary character is autosome dominant hereditary, the point mutation is on the sixth extron of SLC40A1, but this point of mutation is different from those reports published internationally, therefore this gene mutation may be considered as the new type mutation ; 2. The expression of liver hepcidin mRNA of the 3 cases of the family tree members is indicated moving - up, so they occured hepcidin resistance that unable to respond to hepcidin show iron overload.