一例儿童醛固酮和皮质醇共分泌肾上腺瘤的临床表现及全外显子测序分析

Whole-exome sequencing from a case of pediatric aldosterone-and cortisol-coproducing adrenal adenoma

目的对1例儿童醛固酮和皮质醇共分泌瘤患者行全外显子测序,探讨其可能的发病机制。方法收集此例共分泌肾上腺皮质腺瘤患者有关临床资料;提取患者肿瘤组织DNA及外周血DNA,进行全外显子测序,分析胚系及体系突变。结果患者为13岁男孩,因高血压和低血钾就诊;根据临床表现和激素检测的结果,诊断为原发性醛固酮增多症合并亚临床库欣综合征;CT发现右肾上腺4.5 cm×3.6 cm占位,手术病理证实为肾上腺皮质腺瘤。在患者肿瘤组织中发现醛固酮合成酶CTNNB1 c.133T>C(p.S45P)位点突变。未发现KCNJ5、ATP1A1、ATP2B3和CACNA1D等基因突变。结论此例罕见的儿童醛固酮和皮质醇共分泌肾上腺皮质腺瘤的发生与CTNNB1突变有关,但具体机制仍需要进一步研究。

Objective To identify the genetic mutations of aldosterone-and cortisol-coproducing adrenal adenoma in a young boy by whole-exome sequencing.Methods The clinical data of a boy with aldosterone-and cortisol-coproducing adrenal adenoma were collected.Whole-exome sequencing was performed with DNA extracted from the blood and tumor tissue to identify germline and somatic mutations.Results A 13-year-old boy with hypertension and hypokalemia was diagnosed as primary aldosteronism complicated with sub-clinical Cushing's syndrome diagnosed by clinical manifestations and adrenal hormone testing.CT scan found a 4.5 cm×3.6 cm mass in right adrenal gland.The mass was surgically removed and adenoma was proved by pathologic microscopy.A somatic CTNNB1 c.133T>C(p.S45P)mutation was detected in the adenoma tissue.Somatic mutations,such as KCNJ5,ATP1A1,ATP2B3 and CACNA1D were not detected.Conclusions Somatic CTNNB1 mutation is probably the main cause of this rare disease characterized by aldosterone-and cortisol-coproducing adrenal adenoma.But the profound mechanism needs further study.