Low penetrance of a SDHB mutation in a large Dutch paraganglioma family.
Low penetrance of a SDHB mutation in a large Dutch paraganglioma family.
复制标题
DOI：
10.1186/1471-2350-11-92
复制
发表时间：
2010-06-11
影响因子：
--
通讯作者：
Corssmit EP
中科院分区：
文献类型：
--
作者：
Hes FJ;Weiss MM;Woortman SA;de Miranda NF;van Bunderen PA;Bonsing BA;Stokkel MP;Morreau H;Romijn JA;Jansen JC;Vriends AH;Bayley JP;Corssmit EP
琥珀酸脱氢酶亚单位B基因（SDHB）的种系突变使携带者易患副神经节瘤，目前估计突变携带者实际发生肿瘤的机会很高。我们评估了一个大型的临床特征良好的副神经节瘤家族的生殖系SDHB突变的表型和突变率。在一名31岁的索引患者中鉴定出突变后，在突变携带者中进行了广泛的临床筛查，以评估头颈部、胸部和腹部副神经节瘤的存在。对19名家庭成员进行了症状前DNA检测。DNA分析检测到14个进一步的SDHB突变携带者。三个突变携带者（中位年龄78岁）拒绝临床监测，但没有与副神经节瘤相关的临床体征或症状。其余11例突变携带者（平均年龄53岁，范围37-76岁）同意进行临床筛选。只有两个，43岁和48岁，亚临床迷走神经副神经节瘤确定。在这个家族的15个突变携带者中，只有3个发生了副神经节瘤，这导致在48岁时的计算患病率为26%。这个数字低于目前的估计，我们得出的结论是，这个家庭的合作几乎完全实现了突变携带者，并且进行的广泛临床评估使我们能够识别所有受影响的个体。
Germline mutations of the succinate dehydrogenase subunit B gene (SDHB) predispose carriers for paragangliomas, and current estimates of the chance of mutation carriers actually developing tumors (penetrance) are high. We evaluate the phenotype and penetrance of a germline SDHB mutation in a large and clinically well-characterized paraganglioma family. Following identification of the mutation in a 31 year old index-patient, extensive clinical screening was performed in mutation carriers to evaluate the presence of head and neck, thoracic and abdominal paragangliomas. Presymptomatic DNA testing was performed in 19 family members. DNA analysis detected 14 further SDHB mutation carriers. Three mutation carriers (median age 78 years) declined clinical surveillance, but had no clinical signs or symptoms associated with paragangliomas. The remaining 11 mutation carriers (mean age 53, range 37-76 years) consented to clinical screening. In only two, aged 43 and 48 years, were subclinical vagal paragangliomas identified. Only three of the fifteen mutation carriers in this family have developed paraganglioma, which results in a calculated penetrance of 26% at 48 years of age. This figure is lower than current estimates, and we conclude that the co-operation of this family allowed an almost complete attainment of mutation carriers, and the extensive clinical evaluation carried out allowed us to identify all affected individuals.