摘要目的 探讨原发性色素性结节样肾上腺皮质病(PPNAD)所致的库欣综合征患者的诊断要点和遗传学病因.方法 对1例PPNAD患者及其家系进行病史收集及各项相关检查并随访,采集患者及其家系成员共7份全血样本,对PRKAR1A、PDE11A、PDE8B、CTNNB1基因进行测序.结果 先证者(10岁)临床表现为典型库欣综合征,血皮质醇节律消失,尿游离皮质醇偏高,大小剂量地塞米松抑制试验示皮质醇不受抑制,影像学检查示双侧肾上腺结节样增生,手术切除肾上腺组织呈现色素结节样病变及细胞内脂褐素沉着,诊断为PPNAD.家系其他成员无库欣综合征及Carney综合征表现.测序发现先证者PRKAR1A基因一个新的错义突变:C18G,编码的氨基酸由半胱氨酸转变成甘氨酸.先证者父亲及妹妹同为该突变携带者.结论 通过临床及实验室检查,确诊1例PPNAD患者.先证者及2位一级亲属携带相同的PRKAR1A基因突变,提示一新的基因突变导致PPNAD.

abstractsObjective To clarify the clinical features and genetic background of a kindred of primary pigmented nodular adrenocortical disease (PPNAD).Methods Detailed clinical characteristics and laboratory test results from a ten-year old girl diagnosed as PPNAD were collected.Seven members of her family were screened for Cushing syndrome and Carney complex,and their blood DNA was extracted and sequenced for PRKAR1A,PDE11A,PDE8B and CTNNB1 mutations with ABI3730.Results The girl presented with symptoms and signs of hypercortisolism,while no features of Carney complex were observed.Hypercortisolemia,suppressed corticotrophin and high urinary free cortisol level were revealed.Cortisol level could not be suppressed both in high and low dose dexamethasone suppression test.The diagnosis of adrenocorticotrophic hormone (ACTH)-independent Cushing syndrome was established.Image and pathology of adrenal glands were in accordance with PPNAD.Other family members showed no evidence of Cushing syndrome or Carney complex.DNA sequencing showed that the patient harbored a missense mutation,C18G.Her father and younger sister were proved to be carriers of this mutation.Conclusion A Chinese PPNAD family was identified clinically and genetically,and a novel missense mutation of PRKAR1A was found.