多发性内分泌腺瘤2A型家系中ret原癌基因突变的分子筛查

目的探寻2个多发性内分泌腺瘤2A型(MEN2A)家系发病的分子机制。方法提取1982年和1992年中山大学附属第一医院收集的2个MEN2A家系共9名成员外周血基因组DNA,对ret原癌基因21个外显子进行聚合酶链反应(PCR),PCR产物进行直接测序。结果家系1中2例患者存在ret原癌基因exon11的C634R突变,exon2的A45A和exon13的L769L2处多态性;家系2中1例患者存在ret原癌基因C634Y突变,exon2的A45A存在多态性,另外筛查出其子为该基因突变携带者。结论本研究2个家系存在exon11的C634位点突变,达到MEN2A基因水平上的诊断,对其临床治疗及其后代的早期诊断有重要指导意义。

Mutation of the ret proto-oncogene in two Chinese families with multiple endocrine neoplasia type 2A(MEN2A)

Objective To detect ret mutations in two Chinese families with multiple endocrine neoplasia type 2A(MEN2A).Methods In our study,9 members from these two families including 3 patients were recruited.Polymerase chain reaction(PCR)and direct gene sequencing of PCR products by an automated DNA sequencer were applied to scan the entire 21 exons of ret proto-oncogene in the leukocyte DNA of the subjects.Results Two missense mutations were detected in exon11 of the ret proto-oncogene.One was C634R in the 2 patients from a family and the other was C634Y in 2 subjects from another family(one was the patient).Two heterozygous variants(A45A and L769L)in these 4 subjects were revealed.Conclusion Two mutations(C634R and C634Y)are detected in two families with MEN2A.Direct DNA sequencing analysis can diagnose MEN2A at gene level,which is helpful in making clinical management of the disease and in diagnosing earlier in their offspring.