多发性内分泌腺瘤Ⅱa型临床症状及致病基因RET基因突变研究

Clinical symptoms and RET gene mutation analysis of multiple endocrine neoplasia-Ⅱa

目的对2例多发性内分泌腺瘤Ⅱa型(multiple endocrine neoplasia-Ⅱa,MEN-Ⅱa)患者进行RET基因突变检测,用于指导临床实践。方法获得患者知情同意后提取其外周血基因组DNA,采用聚合酶链式反应(polymerase chain reaction,PCR)扩增RET基因的第5、8、10～16外显子,通过产物直接测序来确定患者的突变位点。结果本实验测序结果共发现两处错义杂合突变:1号患者突变位点为第10外显子处的p.C611Y杂合突变;2号患者突变位点为第11外显子处的p.C634R杂合突变,其弟未发现该突变位点。测出的两处错义突变位点经比对人类基因突变库(the human gene mutation database,HGMD)、美国国立生物技术信息中心(national center of biotechnology information,NCBI),证明是已报道的致病突变位点。结论将RET基因基因诊断结果和美国甲状腺协会制定的指南相结合,不仅可以为临床上多发性内分泌腺瘤Ⅱa型患者提供确诊依据,还可以为其家系中携带者制定最佳治疗方案提供参考。

Objective To study the mutation of RET gene in patients with multiple endocrine neoplasia-Ⅱa（MEN-Ⅱa） in order to guide the clinical practice. Methods After the informed consent of the patients was obtained, the genomic DNA of peripheral blood was extracted. Polymerase Chain Reaction（PCR） amplification combined with direct sequencing technology was used to analyze the mutations of disease-causing gene RET in two patients with MEN-Ⅱa. The mutation hotspots of RET gene mainly located in the exon 5,8,10-16. Results In this study, two heterozygous missense mutations were detected by direct sequencing： the heterozygous mutation（p.C611 Y） was located in exon 10 of the patient one＇s gene, while the heterozygous mutation（p.C634 R） was located in exon 11 of the patient two＇s gene, which was not found in her younger brother＇s. Comparing the Human Gene Mutation Database（HGMD） and The National Center for Biotechnology Information（NCBI）, the two missense mutations were proved to be the pathogenic ones which have been reported. ConclusionGenetic diagnosis of RET gene combined with the guide from the American Thyroid Association can provide not only the diagnotic basis for MEN-Ⅱa, but also the reference for making best treatment plan for MEN-Ⅱa carriers.