Genetics of endocrine disease - Clinical and molecular features of the Carney complex: Diagnostic criteria and recommendations for patient evaluation
Genetics of endocrine disease - Clinical and molecular features of the Carney complex: Diagnostic criteria and recommendations for patient evaluation
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DOI：
10.1210/jc.86.9.4041
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发表时间：
2001-09-01
影响因子：
5.8
通讯作者：
Carney, JA
中科院分区：
文献类型：
--
作者：
Stratakis, CA;Kirschner, LS;Carney, JA
Carney综合征是一种以心脏、内分泌、皮肤和神经肿瘤以及各种皮肤和粘膜色素性病变为特征的多发性肿瘤综合征。Carney综合征是一种常染色体显性遗传，可能同时累及多个内分泌腺，如经典的多发性内分泌肿瘤综合征1和2。Carney综合征也与McCuneAlbright综合征有一些相似之处，McCuneAlbright综合征是一种散发性疾病，也以多发性内分泌和非内分泌肿瘤为特征。卡尼综合征与雀斑样痣病和某些错构瘤，特别是Peutz-Jeghers综合征，共有皮肤异常和一些非内分泌肿瘤，与粘膜雀斑样痣病和一种不寻常的性腺肿瘤，大细胞钙化支持细胞瘤。仔细的临床分析，使定位克隆的努力，以确定两个染色体位点窝藏潜在的候选基因卡尼复合体。最近，在17 q22 -24位点，发现编码PKA的1型a调节亚基的肿瘤抑制基因PRKAR 1A在大约一半的已知Carney复合物激酶中突变。PRKAR 1A作为一个典型的肿瘤抑制基因，如在与该复合体相关的肿瘤中17 q22 -24位点的杂合性丢失所证明的。第二个基因座位于染色体2 p16上，大部分（但不是全部）剩余的激酶图谱也参与了Carney复合体肿瘤的分子发病机制，如该基因座的多个遗传变化所示，包括杂合性丢失和拷贝数增加。尽管已知该疾病存在遗传异质性，但临床分析并未检测到PRKAR 1A突变患者与无突变患者之间存在任何相应的表型差异。本文总结了Carney综合征的临床表现，并提出了修订后的诊断标准。根据最近PRKAR 1A基因突变的鉴定，提供了突变率的估计和遗传筛查的建议。
Carney complex is a multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous, and neural tumors, as well as a variety of pigmented lesions of the skin and mucosae. Carney complex is inherited as an autosomal dominant trait and may simultaneously involve multiple endocrine glands, as in the classic multiple endocrine neoplasia syndromes 1 and 2. Carney complex also has some similarities to McCuneAlbright syndrome, a sporadic condition that is also characterized by multiple endocrine and nonendocrine tumors. Carney complex shares skin abnormalities and some nonendocrine tumors with the lentiginoses and certain of the hamartomatoses, particularly Peutz-Jeghers syndrome, with which it shares mucosal lentiginosis and an unusual gonadal tumor, large-cell calcifying Sertoli cell tumor. Careful clinical analysis has enabled positional cloning efforts to identify two chromosomal loci harboring potential candidate genes for Carney complex. Most recently, at the 17q22-24 locus, the tumor suppressor gene PRKAR1A, coding for the type 1 a regulatory subunit of PKA, was found to be mutated in approximately half of the known Carney complex kindreds. PRKAR1A acts a classic tumor suppressor gene as demonstrated by loss of heterozygosity at the 17q22-24 locus in tumors associated with the complex. The second locus, at chromosome 2p16, to which most (but not all) of the remaining kindreds map, is also involved in the molecular pathogenesis of Carney complex tumors, as demonstrated by multiple genetic changes at this locus, including loss of heterozygosity and copy number gain. Despite the known genetic heterogeneity in the disease, clinical analysis has not detected any corresponding phenotypic differences between patients with PRKAR1A mutations and those without. This article summarizes the clinical manifestations of Carney complex from a worldwide collection of affected patients and also presents revised diagnostic criteria for Carney complex. In light of the recent identification of mutations in the PRKAR1A gene, an estimate of penetrance and recommendations for genetic screening are provided.