摘要目的 研究单侧肾上腺增生性原发性醛固酮增多症KCNJ5基因错义突变的情况和意义.方法 收集手术切除并经病理诊断证实的单侧肾上腺增生组织14例,同时收集患者外周血样本,对所有样本的KCNJ5基因编码区进行测序,并预测其蛋白质结构和功能.结果 在14例单侧肾上腺增生组织中发现了3种错义突变:c.451G＞C/A(p.G151R) (2/14)、c.503T＞G(p.L168R) (1/14)、c.830T＞A(p.S209T) (9/14),其中c.830T＞A为新发现的突变.蛋白结构预测显示L168R位于第二跨膜区,后者为保守区;S209位于胞内区,且S209为蛋白激酶(PKC)的磷酸化位点.结论 KCNJ5基因突变与单侧肾上腺增生性原发性醛固酮增多症有关.蛋白质结构预测提示突变可能参与了单侧肾上腺增生的发生和发展.

abstractsObjective To investigate the prevalence of KCNJ5 gene missense mutations and their role in patients with unilateral adrenal hyperplasia (UAH).Methods Fourteen UAH tissues were collected through surgical resection,and all the tissues were confirmed by pathology.Peripheral blood samples of the same patients were collected as control.The coding regions of the KCNJ5 were detected by direct DNA sequencing.Protein structure and function were predicted with specific software.Results Three missense mutations were detected among the 14 patients with UAH,which included c.451G＞C/A (p.G151R) (2/14),c.503T＞G (p.L168R) (1/14),c.830T＞A (p.S209T) (9/14).Among these,c.830T＞A is a newly identified somatic mutation.Protein structure prediction showed that S209T lied in the second transmembrane domain,a conservation region of KCNJ5.S209 was also the phosphorylation site of PKC that is located in intracellular area.Conclusion Missense mutations of KCNJ5 gene may be associated with UAH.Protein structure prediction has suggested that KCNJ5 mutations may be associated with UAH.