Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations
Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations
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DOI：
10.1001/jama.292.8.943
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发表时间：
2004-08-25
影响因子：
120.7
通讯作者：
Eng, C
中科院分区：
文献类型：
--
作者：
Neumann, HPH;Pawlu, C;Eng, C
琥珀酸脱氢酶亚基B （SDHB）和d （SDHD）基因的种系突变分别易导致4型副神经节瘤综合征（PGL-4）和1型副神经节瘤综合征（PGL-1）。在这两种综合征中，嗜铬细胞瘤以及头颈部副神经节瘤都会发生；然而，个体风险和其他临床特征的细节尚不清楚。目的探讨SDHB基因突变携带者与SDHD基因突变携带者临床特征的差异。从2000年4月1日至2004年5月15日，在德国和波兰中部的2个登记处进行了基于人群的SDHB和SDHD生殖系突变遗传筛查，对417例无综合征特征的肾上腺或肾上腺外腹部或胸部嗜铬细胞瘤（n =334）或头颈部副神经节瘤（n =83）患者进行了SDHB和SDHD生殖系突变遗传筛查。主要结局指标：与非突变携带者相比，SDHB与SDHD基因突变的人口学和临床结果。结果417名登记者中有49名（12%）携带SDHB或SDHD突变。此外，在这些携带者的亲属中新检出28例SDHB突变携带者和23例SDHD突变携带者。53例SDHB和47例SDHD总突变携带者的诊断年龄相似，但外显率和肿瘤表现存在差异。头颈部副神经节瘤（10/32 vs 27/34）
Context Germline mutations of the genes encoding succinate dehydrogenase subunits B (SDHB) and D. (SDHD) predispose to paraganglioma syndromes type 4 (PGL-4) and type 1 (PGL-1), respectively. In both syndromes, pheochromocytomas as well as head and neck paragangliomas occur; however, details for individual risks and other clinical characteristics are unknown.Objective To determine the differences in clinical features in carriers of SDHB mutations and SDHD mutations.Design, Setting, and Patients Population-based genetic screening for SDHB and SDHD germline mutations in 417 unrelated patients with adrenal or extra-adrenal abdominal or thoracic pheochromocytomas (n =334) or head and neck paragangliomas (n =83), but without syndromic features, from 2 registries based in Germany and central Poland, conducted from April 1, 2000, until May 15, 2004.Main Outcome Measures Demographic and clinical findings with respect to gene mutation in SDHB vs SDHD compared with nonmutation carriers.Results A total of 49 (12%) of 417 registrants carried SDHB or SDHD mutations. In addition, 28 SDHB and 23 SDHD mutation carriers were newly detected among relatives of these carriers. Comparison of 53 SDHB and 47 SDHD total mutation carriers showed similar ages at diagnosis but differences in penetrance and of tumor manifestations. Head and neck paragangliomas (10/32 vs 27/34, respectively, P