原发性醛固酮增多症（PA）是人类高血压的常见原因。至少 80% 的产生醛固酮的腺瘤中发现了 KCNJ5、CACNA1D、ATP1A1 和 ATP2B3 的体细胞突变，这些突变会导致人类单侧 PA。其他 7 个基因中很少发现体细胞突变；在发现它们的突变之前，很少有人知道它们在醛固酮分泌中发挥作用。研究家猫（已知也会发生自发性 PA）的体细胞突变，可能会增进对正常肾上腺生理学和 PA 病理生理学的理解。从 13 只患有单侧醛固酮分泌肿瘤的猫的组织中提取 DNA 和 RNA，包括对 8 种癌症和 5 种腺瘤进行了全基因组测序、靶向桑格测序和 RNA 测序。过滤单核苷酸取代变体，以选择那些对蛋白质功能具有预测有害作用并怀疑在醛固酮分泌中起作用的变体。在 3 个腺瘤和 2 个癌中发现了可能的功能性体细胞单核苷酸多态性 (n = 8)。在人类 PA 中也发生突变的 2 个基因中发现了具有预测显着影响的突变； GNAQ 和 CTNNB1，以及 CACNA1C 的残基中类似于常见的 CACNA1D 突变。与人类相比，在猫肿瘤和非肿瘤肾上腺组织中，CACNA1C 的表达量远高于 CACNA1D。在 KCNJ5、CACNA1D、ATP1A1 或 ATP2B3 中未发现突变。在猫中发现了与人类中发现的类似突变。因此，这两个物种很可能都面临着增加醛固酮分泌的突变的潜在选择压力。

Primary aldosteronism (PA) is a common cause of human hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 are found in at least 80% of aldosterone-producing adenomas, which cause unilateral PA in humans. Somatic mutations have been identified infrequently in 7 other genes; few of these were known to play a role in aldosterone secretion before the discovery of their mutations. Interrogating somatic mutations in the domestic cat, in which spontaneous PA is also known to occur, might improve the understanding of normal adrenal gland physiology and the pathophysiology of PA.DNA and RNA extracted from tissue from 13 cats with unilateral aldosterone-secreting tumors, including 8 carcinomas and 5 adenomas, underwent whole genome sequencing, targeted Sanger sequencing, and RNA sequencing. Single-nucleotide substitution variants were filtered to select those with a predicted deleterious effect on protein function and a suspected role in aldosterone secretion.Probable functional somatic single-nucleotide polymorphisms (n=8) were found in 3 adenomas and 2 carcinomas. Mutations with predicted significant effects were identified in 2 genes also mutated in human PA; GNAQ and CTNNB1, and in a residue of CACNA1C analogous to a common CACNA1D mutation. In contrast to humans, CACNA1C expression was much greater than CACNA1D in both feline tumor and nontumor adrenal tissue. No mutations were identified in KCNJ5, CACNA1D, ATP1A1, or ATP2B3.Similar mutations were identified in cats to those found in humans. It is, therefore, likely that both species have shared underlying selection pressures for mutations that increase aldosterone secretion.