Chan L F, Clark A J L, Metherell L A
Centre for Endocrinology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London, UK.
Horm Res. 2008;69(2):75-82. doi: 10.1159/000111810. Epub 2007 Dec 5.
Familial glucocorticoid deficiency (FGD), otherwise known as hereditary unresponsiveness to ACTH, is a rare autosomal recessive disease characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. Mutations of the ACTH receptor, also known as the melanocortin-2 receptor (MC2R), account for approximately 25% of FGD cases. More recently a second gene, MRAP (melanocortin-2 receptor accessory protein), was identified and found to account for a further 15-20%. MRAP encodes a small single transmembrane domain protein, which is essential in the trafficking of the MC2R to the cell surface. In this review, we will firstly summarize the clinical presentation and genetic aetiology of this condition. Secondly, we will discuss how the discovery of MRAP has enhanced our understanding of the mechanisms of ACTH/MC2R action. Finally, we will explore future developments in this field.
家族性糖皮质激素缺乏症（FGD），又称遗传性促肾上腺皮质激素无反应性，是一种罕见的常染色体隐性疾病，其特征是在无盐皮质激素缺乏的情况下出现糖皮质激素缺乏。促肾上腺皮质激素受体（又称黑皮质素-2受体，MC2R）的突变约占FGD病例的25%。最近，另一个基因MRAP（黑皮质素-2受体辅助蛋白）被发现，其突变又占15%-20%。MRAP编码一种小的单跨膜结构域蛋白，该蛋白对于MC2R转运至细胞表面至关重要。在本综述中，我们首先将总结这种疾病的临床表现和遗传病因。其次，我们将讨论MRAP的发现如何增进了我们对促肾上腺皮质激素/MC2R作用机制的理解。最后，我们将探索该领域未来的发展。
