Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Germany.
Hypertension. 2022 May;79(5):887-897. doi: 10.1161/HYPERTENSIONAHA.121.16498. Epub 2022 Feb 10.
Primary aldosteronism is considered the commonest cause of secondary hypertension. In affected individuals, aldosterone is produced in an at least partially autonomous fashion in adrenal lesions (adenomas, [micro]nodules or diffuse hyperplasia). Over the past decade, next-generation sequencing studies have led to the insight that primary aldosteronism is largely a genetic disorder. Sporadic cases are due to somatic mutations, mostly in ion channels and pumps, and rare cases of familial hyperaldosteronism are caused by germline mutations in an overlapping set of genes. More than 90% of aldosterone-producing adenomas carry somatic mutations in K channel Kir3.4 (), Ca channel Ca1.3 (), alpha-1 subunit of the Na/K ATPase (), plasma membrane Ca transporting ATPase 3 (), Ca channel Ca3.2 (), Cl channel ClC-2 (), β-catenin (), and/or G-protein subunits alpha q/11 (). Mutations in some of these genes have also been identified in aldosterone-producing (micro)nodules, suggesting a disease continuum from a single cell, acquiring a somatic mutation, via a nodule to adenoma formation, and from a healthy state to subclinical to overt primary aldosteronism. Individual glands can have multiple such lesions, and they can occur on both glands in bilateral disease. Familial hyperaldosteronism, typically with early onset, is caused by germline mutations in steroid 11-beta hydroxylase/ aldosterone synthase (), , , , and .
原醛症被认为是继发性高血压最常见的原因。在受影响的个体中，醛固酮至少部分自主地在肾上腺病变（腺瘤、微结节或弥漫性增生）中产生。在过去的十年中，下一代测序研究使人们认识到原醛症主要是一种遗传疾病。散发性病例归因于体细胞突变，主要发生在离子通道和泵中，而罕见的家族性醛固酮增多症是由重叠基因的种系突变引起的。超过 90%的产生醛固酮的腺瘤携带 K 通道 Kir3.4 ()、钙通道 Ca1.3 ()、Na/K ATP 酶的α-1 亚基 ()、质膜钙转运 ATP 酶 3 ()、钙通道 Ca3.2 ()、氯离子通道 ClC-2 ()、β-连环蛋白 () 和/或 G 蛋白亚基αq/11 () 的体细胞突变。这些基因中的一些突变也已在产生醛固酮的（微）结节中被发现，这表明从单个细胞获得体细胞突变，通过结节形成腺瘤，从健康状态到亚临床状态到显性原醛症，存在疾病连续体。单个腺体可以有多个这样的病变，并且在双侧疾病中它们可以同时发生在两个腺体上。家族性醛固酮增多症，通常发病较早，是由类固醇 11-β羟化酶/醛固酮合酶 ()、、、、和的种系突变引起的。
