摘要
目的检测一个多发性内分泌腺瘤病（MEN）2A型家系中RET原癌基因的突变情况。方法观察一个MEN2A家系成员的表型，并对与MEN相关的且点突变率较高的RET原癌基因第10和11外显子进行PCR产物直接DNA测序以了解其杂合性。结果家系中4名家族成员均存在RET原癌基因第11外显子Cys（TGC）634Arg（CGC）错义突变和GIy（GGT）691Ser（AGT）的单核苷酸多态性，另有1名成员仅存在RET原癌基因Gly（GGT）691Ser（AGT）的单核苷酸多态性。经B超检查发现其中2名成员双侧甲状腺及一侧肾上腺和一侧甲状旁腺有实性占位病变，1名成员双侧甲状腺及一侧肾上腺有实性占位病变，1名成员双侧甲状腺、双侧肾上腺和一侧甲状旁腺有实性占位病变，1名成员仅有甲状腺多发性小结节。另外有3名成员B超检查有异常，但无基因突变。结论对MEN2A家系的基因分析证实RET原癌基因第11外显子634位密码子存在突变和（或）691位密码子存在单核苷酸多态性，对MEN2A能在基因水平作出诊断。
Objective To detect mutations of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A （MEN2A）. Methods Nineteen family members were recruited in the study. The phenotype of the members with MEN2A were observed. PCR was performed to amplify exons 10 and 11 of the RET protooncogene. The PCR products were purified and a direct DNA sequence analysis was performed. Results The Cys （ TGC ） 634Arg （CGC） missense mutation and Gly （ GGT ） 691 Set （AGT） in exon 11 of the RET proto-oncogene were both detected in four members of the family. Only the polymorphism Gly691Ser in exon 11 of the RET protooncogene was detected in one member. The results of the ultrasound examination were shown as follows： two members with bilateral thyroid, one side of parathyroid and adrenal solid lesions; one member with bilateral thyroid and one iside of adrenal solid lesions; one member with bilateral thyroid and adrenal and one side of parathyroid solid lesions; and one member with multiple thyroid small nodules. Additionally, another three members with abnormal findings on ultrasound examinations had no gene mutation. Conclusion Analysis of RET gene identifies a TGC to CGC mutation at codon 634 and the polymorphism Gly691Ser in exon 11 in this family with MEN2A. Direct DNA sequencing analysis is useful in diagnosis of MEN2A at gene level.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2008年第6期626-629,共4页
Chinese Journal of Endocrinology and Metabolism
