CAJ | 학술논문

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.
목적 탐토원발성색소성결절양신상선피질병(PPNAD)소치적고흔종합정환자적진단요점화유전학병인.방법 대1례PPNAD환자급기가계진행병사수집급각항상관검사병수방,채집환자급기가계성원공7빈전혈양본,대PRKAR1A、PDE11A、PDE8B、CTNNB1기인진행측서.결과 선증자(10세)림상표현위전형고흔종합정,혈피질순절률소실,뇨유리피질순편고,대소제량지새미송억제시험시피질순불수억제,영상학검사시쌍측신상선결절양증생,수술절제신상선조직정현색소결절양병변급세포내지갈소침착,진단위PPNAD.가계기타성원무고흔종합정급Carney종합정표현.측서발현선증자PRKAR1A기인일개신적착의돌변:C18G,편마적안기산유반광안산전변성감안산.선증자부친급매매동위해돌변휴대자.결론 통과림상급실험실검사,학진1례PPNAD환자.선증자급2위일급친속휴대상동적PRKAR1A기인돌변,제시일신적기인돌변도치PPNAD.
Objective 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.