Pediatric Endocrinology Unit, Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris Descartes University, 82, Avenue Denfert Rochereau, 75014 Paris, France.
Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):389-99. doi: 10.1016/j.beem.2010.03.003.
Carney complex (CNC) is a rare multiple familial neoplasia syndrome that is characterized by multiple types of skin tumors and pigmented lesions, endocrine neoplasms, myxomas and schwannomas and is inherited in an autosomal dominant manner. Clinical and pathologic diagnostic criteria are well established. Over 100 pathogenic variants in the regulatory subunit type 1A (RI-A) of the cAMP-dependent protein kinase (PRKAR1A) have been detected in approximately 60% of CNC patients, most leading to R1A haploinsufficiency. Other CNC-causing genes remain to be identified. Recent studies provided some genotype-phenotype correlations in CNC patients carrying PRKAR1A-inactivating mutations, which provide useful information for genetic counseling and/or prognosis; however, CNC remains a disease with significant clinical heterogeneity. Recent mouse and in vitro studies have shed light into how R1A haploinsufficiency causes tumors. PRKAR1A defects appear to be weak tumorigenic signals for most tissues; Wnt signaling activation and cell cycle dysregulation appear to be important mediators of the tumorigenic effect of a defective R1A.
卡尼综合征（CNC）是一种罕见的多发性家族性肿瘤综合征，其特征是多种皮肤肿瘤和色素病变、内分泌肿瘤、黏液瘤和雪旺细胞瘤，呈常染色体显性遗传。临床和病理诊断标准已经确立。在大约 60%的 CNC 患者中已经检测到环磷酸腺苷依赖性蛋白激酶（PRKAR1A）调节亚基 1A（RI-A）的 100 多种致病性变异，大多数导致 R1A 单倍不足。其他 CNC 致病基因仍有待确定。最近的研究为携带 PRKAR1A 失活突变的 CNC 患者提供了一些基因型-表型相关性，为遗传咨询和/或预后提供了有用的信息；然而，CNC 仍然是一种具有显著临床异质性的疾病。最近的小鼠和体外研究揭示了 R1A 单倍不足如何导致肿瘤。PRKAR1A 缺陷似乎对大多数组织都是较弱的致癌信号；Wnt 信号激活和细胞周期失调似乎是 R1A 缺陷致癌效应的重要介质。
