一多发性内分泌腺瘤病2A型家系的临床调查及基因分析

Clinical investigation and gene analysis of one pedigree with multiple endocrine neoplasia type 2A

目的进行一多发性内分泌腺瘤病2A型家系的临床调查及基因分析。方法对一个包括先证者在内共24位成员的MEN2A家系进行临床调查,并提取16位成员外周血基因组DNA,对RET基因的第10、11外显子进行PCR扩增,PCR产物进行直接测序。结果 (1)除先证者外,该家系有1例患者曾诊断MEN2A,但拒绝抽血检查;3例疑似患者已死亡,无法进行基因分析;筛查出1名成员为基因突变携带者,后该成员于家中突发胸闷、面色苍白死亡;(2)经RET基因突变检查证实,该先证者及1名家系成员存在10q 11.2外显子11(密码子634)RET基因点突变:Cys634Arg。结论本研究该家系存在外显子11的C634位点突变,应常规对所有MEN2A患者及其家系高危成员尽早进行基因突变分析和筛查。

Objective To carry out a clinical investigation and gene analysis of one pedigree with multiple endocrine neoplasia type 2A（MEN2A）.Methods The DNAs of the 16 members from the family were extracted from peripheral leukocytes,PCR and gene sequencing of PCR products by an automated DNA sequencer was applied to scan the exon 10 and 11 of the RET proto-oncogene.Results（1）The pedigree of this index case had one patient with multiple endocrine neoplasia type 2A,who refused to be phlebotomized for examining;Three doubtful patients died,so could not have the gene analysis;Genetic screening identified the same mutation in a family member,who then died with chest distress and pallor suddenly at home.（2）A missense mutation of TGC（Cys） to CGC（Arg） at codon 634 in exon 11 of the RET proto-oncogene was detected in the index case and a family member.Conclusion The mutation（C634R） was detected in the family with MEN2A.Early RET mutation analysis should be performed routinely in all MEN2A,and screening methods might be used for analyzing family members at risk.