一个多发性内分泌腺瘤病2A型家系新的RET原癌基因突变方式  

A novel RET proto-oncogene mutation in a pedigree of multiple endocrine neoplasia type 2A

作　　者：张少玲[1] 翁育[1] 严励[1] 姜晓华[2] 黎锋[1] 陈黎红[1] 李焱[1] 程桦[1] 

机构地区：[1]中山大学附属第二医院内分泌科,广州510120 [2]上海交通大学医学院附属瑞金医院内分泌代谢病科

出　　处：《中华内分泌代谢杂志》2008年第3期282-286,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：“十五”国家科技攻关计划（2004BA720A29）;广州市科委科技攻关计划（2005Z3-C7601）.志谢 感谢上海交通大学医学院附属瑞金医院内分泌代谢病科宁光教授、李小英教授所提供的引物和相关技术指导.感谢中山大学附属第二医院超声科罗葆明主任为此家系调查和随访所作的超声检查.

摘　　要：目的探讨一个多发性内分泌腺瘤病2A型（MEN2A）家系的临床表现和RET原癌基因突变方式。方法对一个MEN2A家系成员进行临床调查，提取其中3例具有典型临床表现的患者及15个家庭成员的外周血淋巴细胞DNA，对RET原癌基因的第8、10、11、13～16外显子进行DNA测序分析，并对发现突变的PCR产物进行亚克隆测序。结果该家系先证者系30岁起先后确诊为嗜铬细胞瘤和甲状腺髓样癌的男性，其一姐患有嗜铬细胞瘤、一弟患有甲状腺髓样癌。在这3例患者及另外2例未发病的家庭成员中，发现了RET原癌基因第11号外显子存在相同的杂合突变，即1893-1895delCGA，系一种新的突变类型。结论RET原癌基因第11号外显子1893—1895delCGA杂合突变，是一种新突变，可能为该MEN2A家系的致病基因。Objective To observe the clinical manifestation and the mode of RET proto-oncogene mutation in a pedigree of mutiple endocrine neoplasia type 2A （MEN2A）. Methods Genomic DNA was extracted from the peripheral blood lymphocytes in 18 family members including 3 patients, then PCR was performed to amplify seven exons of the RET proto-oncogene, i.e. exon 8, I0, II, 13-16. The PCR products were directly sequenced to identify the RET mutation and then sequenced after subcloning to identify their heterozygosity. Results The male proband suffered from pheochromocytoma and medullary thyroid carcinoma since the age of 30; while his sibling sister was ill with pheochromocytoma, and his brother with medullary thyroid carcinoma. A novel heterozygous mutation, 1893-1895delCGA, was detected in exon 11 of the RET proto-oncogene in the 3 patients and the other 2 family members. Conclusion A novel heterozygous mutation of RET proto-oncogene, 1893-1895delCGA, seems to be the disease-causing mutation in the studied MEN2A family.

关 键 词：多发性内分泌腺瘤病2A型 嗜铬细胞瘤 RET原癌基因 

分 类 号：R736[医药卫生—肿瘤] R736.1[医药卫生—临床医学]