一例多发性内分泌腺瘤病2A型家系的临床特征及RET基因突变

Clinical features and mutations of RET proto-oncogene in a pedigree affected with type 2A multiple endocrine neoplasia

目的探讨一例多发性内分泌腺瘤病2A型（multiple endocrine neoplasia type2A，MEN2A）家系的临床特征及其RET基因的突变情况。方法对该家系进行系统的临床调查，提取其成员外周血基因组DNA，用PCR扩增RET原癌基因的第8、10、11、13、14、15、16外显子并进行双向测序。结果家系内8名患者存在,RET基因第11外显子p．C634W的杂合性点突变。3人被诊断为嗜铬细胞瘤，1人被诊断为甲状腺髓样癌，1人被诊断为嗜铬细胞瘤合并甲状腺髓样癌，1人被诊断为甲状腺髓样癌合并甲状旁腺功能亢进，1人体检发现甲状腺肿大但拒绝诊治，还发现1例突变携带者。结论患者家系存在RET基因的p．C634W突变，多数携带者已发展为甲状腺髓样癌及／或嗜铬细胞瘤。为早期诊治，应该对MEN2A家系成员尽早进行基因突变筛查。

Objective To investigate the clinical features and mutations of RET proto-oncogene in a pedigree affected with multiple endocrine neoplasia type 2A （MEN 2A）. Methods Clinical data of the family members was collected. Genomic DNA from peripheral blood [eukocytes were extracted and subjected to PCR amplification. Exons 8, 10, 11, 13, 14, 15, 16 of the RET gene was sequenced. Results A missense mutation p. C634W was detected in 8 members from the family. Among them, 3 were diagnosed with pheochromocytoma, 1 with medullary thyroid carcinoma, 1 with medullary thyroid carcinoma and pheochromocytoma, 1 with medullary thyroid carcinoma and hyperparathyroidism. One member was found with thyroid enlargement but refused further examination, and another one was identified as carrier of the RET gene mutation. Conclusion A p. C634W mutation has been detected in a family affected with MEN2A, in which most carriers have developed clinical symptoms. RET mutation detection should be routinely performed for families affected with MEN2A.