Griffiths W J H
Department of Hepatology, Cambridge University Teaching Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge, UK.
Aliment Pharmacol Ther. 2007 Aug 1;26(3):331-42. doi: 10.1111/j.1365-2036.2007.03387.x.
Since the seminal discovery of the HFE gene a decade ago, considerable further progress in unravelling the genetic basis of haemochromatosis has been made. Novel genes and iron overload phenotypes have been described with potential insights into the molecular pathophysiology of human iron metabolism.
To review recent key advances in the field of inherited iron overload and assess their impact on clinical practice and on our understanding of iron regulation.
A PubMed search was undertaken predominantly using 'haemochromatosis', 'HFE', 'hepcidin' and 'ferroportin'. Illustrative cases were sought.
The impact of HFE mutation analysis on the management of haemochromatosis is significant and allows early accurate diagnosis. HFE is also implicated in the siderosis associated with other liver pathologies. Non-HFE genes underpinning other forms of haemochromatosis are now recognized and genotype-phenotype interactions result in a spectrum of disease. These novel gene products interact with HFE in a common pathway for iron homeostasis.
Further identification of non-HFE genes associated with iron homeostasis will enhance our diagnostic certainty of primary haemochromatosis and may explain the variable expression seen in HFE-related disease. Improving our understanding of the mechanisms of iron regulation may lead to novel therapeutic strategies for the management of iron overload.
自十年前发现HFE基因以来，在揭示血色素沉着症的遗传基础方面已取得了相当大的进一步进展。已描述了新的基因和铁过载表型，对人类铁代谢的分子病理生理学有了潜在的深入了解。
回顾遗传性铁过载领域的近期关键进展，并评估它们对临床实践以及我们对铁调节理解的影响。
主要使用“血色素沉着症”“HFE”“铁调素”和“铁转运蛋白”在PubMed上进行检索。寻找具有代表性的病例。
HFE突变分析对血色素沉着症的管理具有重要意义，可实现早期准确诊断。HFE还与其他肝脏疾病相关的铁沉积有关。现在已经认识到支撑其他形式血色素沉着症的非HFE基因，并且基因型-表型相互作用导致了一系列疾病。这些新的基因产物在铁稳态的共同途径中与HFE相互作用。
进一步鉴定与铁稳态相关的非HFE基因将提高我们对原发性血色素沉着症的诊断确定性，并可能解释HFE相关疾病中所见的可变表达。增进我们对铁调节机制的理解可能会带来治疗铁过载的新策略。
