Department of Urology, Chinese PLA General Hospital, Beijing, China.
Fam Cancer. 2013 Dec;12(4):657-67. doi: 10.1007/s10689-013-9642-y.
ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare disorder characterized by bilateral macronodular hyperplasia of the adrenal glands and increased cortisol production with subclinical or overt Cushing's syndrome. Although the family clustering of AIMAH is infrequent, we have tried our best to find such a familial affected pedigree with complete clinical information and successfully collect adrenalectomy tissue samples from two members of this family. Using whole exome sequencing and several variant prioritization strategies based on disease network analysis, we identified Endothelin receptor type A (EDNRA) Ser420Thr mutation as a causative mutation of AIMAH. EDNRA is a member of G protein coupled receptor family and is involved in cardiovascular or polycystic kidney disease. Our findings indicate that the mutation of EDNRA at S420T site should be regard as a potential AIMAH causative variation in familial and sporadic affected patients.
促肾上腺皮质激素（ACTH）非依赖性大结节性肾上腺增生症（AIMAH）是一种罕见疾病，其特征为双侧肾上腺大结节性增生和皮质醇产生增加，并伴有亚临床或显性库欣综合征。虽然 AIMAH 的家族聚集现象并不常见，但我们已尽力寻找这样一个具有完整临床信息的家族性受累家系，并成功从该家系的两名成员中收集了肾上腺切除术组织样本。使用全外显子组测序和几种基于疾病网络分析的变异优先级策略，我们鉴定出内皮素受体 A 型（EDNRA）Ser420Thr 突变是 AIMAH 的致病突变。EDNRA 是 G 蛋白偶联受体家族的成员，参与心血管疾病或多囊肾病。我们的研究结果表明，S420T 位点的 EDNRA 突变应被视为家族性和散发性受累患者中潜在的 AIMAH 致病变异。
