两个多发性内分泌腺瘤病2A型家系RET基因突变研究

The study of the RET proto-oncogene mutation in 2 pedigrees of multiple endocrine neoplasia type 2A

目的总结2个多发性内分泌腺瘤病2A(MEN2A)型家系的临床特点,及MEN2A家系RET基因突变类型。方法对2个MEN2A家系进行临床调查,分析其临床特点。提取2个家系成员外周血基因组DNA,扩增先证者RET原癌基因的外显子10、11,13-16,并行Sanger测序,测得突变所在的外显子后,将其亲属相应外显子的扩增产物进行测序。结果家系1的先证者及其哥哥的10q 11.2外显子11(密码子634)RET原癌基因发生点突变:Cys643Trp。家系2的先证者其兄长存在10q 11.2外显子11(密码子634)RET原癌基因发生点突变:Cys643Arg,筛查出1个家系成员为基因突变携带者。结论 RET原癌基因第11外显子Cys643Trp杂合突变及Cys634Arg杂合突变,均为MEN2A的致病基因,此2个家系患者虽然突变类型不同,但两家系患者在起病方式、发病年龄及临床表现均相似。基因检测是诊断MEN2A的有效方法。

Objective To analyze the clinical features and explore the mutations of the RET proto-oneogene of two pedigrees with multiple endocrine neoplasia type 2A （MEN2A） suggested by clinical manifestations. Methods A clinical investigation and clinical features analysis of two pedigrees with multiple endocrine neoplasia type 2A （MEN2A） were carried out. Genomic DNA was extracted from the peripheral blood lymphocytes in family members of the 2 pedigrees. Then PCR was performed to amplify six exons of the RET proto-oncogene, that is, exonl0, 11, 13, 14, 15, 16 for the two probands.PCR products were purified and then analyzed by Sanger sequencing analysis.According to the sites of the gene mutation of the two probands,their family members were underwent genetic testing accordingly. Results A mis-sense mutation of Cys643Trp in exon 11 of the RET proto-oncogene was detected in the index case and his brother who presented with a thyroid mass of pedigree 1. Cys634Arg was detected in exon 11 of the RET proto-oneogene in the 2 patients and another family member of pedigree 2. Conclusion The germline mutations of RET proto-oncogene Cys643Trp and Cys634Arg may be the disease-causing mutations of the 2 MEN2A families.Although the gene mutations of RET proto-oncogene in the 2 pedigrees are different, the clinical features between them related to their mutations seems to be similar. Direct DNA sequencing analysis can diagnose MEN2A at gene level, which is helpful for clinical management of the disease and in earlv diagnosis in their offstMn^s.