Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency.
Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency.
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DOI：
10.1111/j.1365-2265.2008.03511.x
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发表时间：
2009-08
影响因子：
3.2
通讯作者：
Clark AJ
中科院分区：
文献类型：
--
作者：
Chan LF;Metherell LA;Krude H;Ball C;O'Riordan SM;Costigan C;Lynch SA;Savage MO;Cavarzere P;Clark AJ
家族性糖皮质激素缺乏症（FGD）是一种罕见的常染色体隐性遗传病，其特征是孤立性糖皮质激素缺乏症伴盐皮质激素分泌保留。ACTH受体（MC 2 R）突变约占所有FGD病例的25%，但由于这些通常是错义突变，因此通常保留一定程度的受体功能。然而，最近的一份报告表明，在一些可能更严重的MC 2 R突变患者中观察到了肾素-醛固酮轴的紊乱。此外，MC 2 R基因敲除小鼠尽管保留了正常肾小球，但仍具有明显的醛固酮缺乏症和高钾血症。我们希望确定一组具有MC 2 R严重无义突变的患者是否表现出盐皮质激素缺乏的证据，从而挑战FGD的传统诊断特征，这可能导致诊断错误分类。无义MC 2 R突变患者的临床回顾。在1993年至2008年期间，对164名FGD患者进行了MC 2 R突变筛查。共发现42例患者（34个家系）MC 2 R基因突变。其中，6例患者（4个家族）被发现有纯合无义或移码突变。6例患者中有4例出现轻度的肾素-血管紧张素-醛固酮轴紊乱，范围从血浆肾素水平轻微升高到低醛固酮水平，尽管没有发现明显的盐皮质激素缺乏或电解质紊乱，没有患者需要氟氢可的松替代治疗。严重的无义和移码MC 2 R突变与临床上显著的盐皮质激素缺乏无关，因此不太可能需要长期盐皮质激素替代。
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for approximately 25% of all FGD cases, but since these are usually missense mutations, a degree of receptor function is frequently retained. A recent report, however, suggested that disturbances in the renin–aldosterone axis were seen in some patients with potentially more severe MC2R mutations. Furthermore, MC2R knock out mice have overt aldosterone deficiency and hyperkalaemia despite preservation of a normal zona glomerulosa. We wished to determine whether a group of patients with severe nonsense mutations of the MC2R exhibited evidence of mineralocorticoid deficiency, thereby challenging the conventional diagnostic feature of FGD which might result in diagnostic misclassification. Clinical review of patients with nonsense MC2R mutations. Between 1993 and 2008, 164 patients with FGD were screened for mutations in the MC2R. Totally 42 patients (34 families) were found to have mutations in the MC2R. Of these, 6 patients (4 families) were found to have homozygous nonsense or frameshift mutations. Mild disturbances in the renin–angiotensin–aldosterone axis were noted in four out of six patients, ranging from slightly elevated plasma renin levels to low aldosterone levels, although frank mineralocorticoid deficiency or electrolyte disturbance were not found. No patient required fludrocortisone replacement. Severe nonsense and frameshift MC2R mutations are not associated with clinically significant mineralocorticoid deficiency and are thus unlikely to require long-term mineralocorticoid replacement.
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影响因子：
3.2
作者：
Lin L;Hindmarsh PC;Metherell LA;Alzyoud M;Al-Ali M;Brain CE;Clark AJ;Dattani MT;Achermann JC
通讯作者：
Achermann JC
影响因子：
5.8
作者：
Naville, D;Barjhoux, L;Begeot, M
通讯作者：
Begeot, M
影响因子：
15.9
作者：
TSIGOS, C;ARAI, K;CHROUSOS, GP
通讯作者：
CHROUSOS, GP
DOI：
10.1016/j.beem.2006.09.002
发表时间：
2006-12-01
影响因子：
7.4
作者：
Metherell, Louise A.;Chan, Li F.;Clark, Adrian J. L.
通讯作者：
Clark, Adrian J. L.
家族性糖皮质激素缺乏症 1 型中发现的大多数促肾上腺皮质激素受体（黑皮质素 2 受体）突变会导致受体向细胞表面的运输缺陷。
影响因子：
5.8
作者：
Chung, T. T.;Webb, T. R.;Chan, L. F.;Cooray, S. N.;Metherell, L. A.;King, P. J.;Chapple, J. P.;Clark, A. J. L.
通讯作者：
Clark, A. J. L.