Ferroportin disease: a systematic meta-analysis of clinical and molecular findings.
Ferroportin disease: a systematic meta-analysis of clinical and molecular findings.
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DOI：
10.1016/j.jhep.2010.05.016
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发表时间：
2010-11
影响因子：
25.7
通讯作者：
Zoller H
中科院分区：
文献类型：
--
作者：
Mayr R;Janecke AR;Schranz M;Griffiths WJ;Vogel W;Pietrangelo A;Zoller H
经典的膜铁转运蛋白病的特征是高铁蛋白血症、正常的转铁蛋白饱和度和巨噬细胞中的铁过载。非经典形式的特征在于额外的肝细胞铁沉积和高转铁蛋白饱和度。这两种形式都表现为常染色体显性遗传，并与ferroportin基因（SLC40A1）突变有关。SLC40A1编码在巨噬细胞、肠细胞和肝细胞中表达的细胞铁输出蛋白。该分析的目的是确定SLC40A1突变的突变率，并评估计算机模拟工具，以预测膜铁转运蛋白突变的功能障碍，作为体外研究的替代方法。我们进行了系统的文献回顾和荟萃分析的生化表现，遗传学和病理学的ferroportin疾病。在报告的176名SLC 40 A1突变个体中，80名被归类为典型表型，具有高铁蛋白血症和正常转铁蛋白饱和度。53例患者表现为高铁蛋白血症和转铁蛋白饱和度升高的非经典表型。其余患者血清铁蛋白正常或数据报告不完整。尽管所有活检患者的肝铁浓度增加，但仅11%的患者存在显著的纤维化或肝硬化。高铁蛋白血症存在于86%的个体与ferroportin突变。膜铁转运蛋白突变的生物信息学分析表明，PolyPhen评分对于膜铁转运蛋白突变和多态性之间的区分具有99%的灵敏度和67%的特异性。与HFE血色素沉着症相比，膜铁转运蛋白病具有高发病率，遗传异质性，很少与纤维化相关。非经典的膜铁转运蛋白疾病与纤维化的风险较高和更严重的肝铁超载有关。
Classical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages, enterocytes, and hepatocytes. The aim of the analysis is to determine the penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the functional impairment of ferroportin mutations as an alternative to in vitro studies. We conducted a systematic review of the literature and meta-analysis of the biochemical presentation, genetics, and pathology of ferroportin disease. Of the 176 individuals reported with SLC40A1 mutations, 80 were classified as classical phenotype with hyperferritinemia and normal transferrin saturation. The non-classical phenotype with hyperferritinemia and elevated transferrin saturation was present in 53 patients. The remaining patients had normal serum ferritin or the data were reported incompletely. Despite an increased hepatic iron concentration in all biopsied patients, significant fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in 86% of individuals with ferroportin mutations. Bio-informatic analysis of ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and a specificity of 67% for the discrimination between ferroportin mutations and polymorphisms. In contrast to HFE hemochromatosis, ferroportin disease has a high penetrance, is genetically heterogeneous and is rarely associated with fibrosis. Non-classical ferroportin disease is associated with a higher risk of fibrosis and a more severe overload of hepatic iron.
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影响因子：
9.8
作者：
Easton, Douglas F.;Deffenbaugh, Amie M.;Goldgar, David E.
通讯作者：
Goldgar, David E.
影响因子：
2.3
作者：
Bach, V;Remacha, A;Baiget, M
通讯作者：
Baiget, M
影响因子：
9.3
作者：
Cunat, Severine;Giansily-Blaizot, Muriel;Aguilar-Martinez, Patricia
通讯作者：
Aguilar-Martinez, Patricia
影响因子：
13.5
作者：
Griffiths, William J. H.;Mayr, Roman;Cox, Timothy M.
通讯作者：
Cox, Timothy M.
影响因子：
20.3
作者：
Drakesmith, H;Schimanski, LM;Townsend, ARM
通讯作者：
Townsend, ARM