一个多发性内分泌腺瘤病1型家系MEN1基因突变的研究

Detection of the mutation of MEN1 gene in a pedigree with multiple endocrine neoplasia type 1

目的检测一个多发性内分泌腺瘤病1型家系的MEN1基因突变情况。方法提取12名家系成员外周血基因组DNA，对MEN1基因所有10个外显子进行聚合酶链反应及产物直接测序，亚克隆测序鉴定其杂合性。结果家系中1例病理确诊甲状旁腺增生的患者存在MEN1基因第10外显子突变1649—1650insC，导致密码子514发生移码突变，另外筛盒出2名家系成员也为该突变携带者，临床检测符合MEN1诊断标准。结论存多发性内分泌腺瘤病1型中国人家系中检测出MEN1基因杂合突变1649—1650insC，该突变在中国人尚未见报道，同时，对家系成员进行基因筛查可以早期诊断该疾病。

Objective To deetect the mutation of the MEN1 gene in a pedigree with multiple endocrine neoplasia type 1 （MEN 1 ）. Methods Twelve family members were recruited to this study. Peripheral blood was collected and total genomic DNA was prepared for PCR. PCR products of all 10 exons in MEN1 gene were purified and a direct gene sequence analysis was performed. Subclone sequencing was performed to identify the heterozygosity. Results A one base pair of insertion（ 1649 1650insC） in exon 10 of MEN1 gene,resulting in a frameshift mutation of codon 514, was detected in a patient with parathyroid hyperplasia diagnosed by pathology. Genetic screening identified the same mutation in other 2 family members and the results of clinical detection were consistent with the diagnostic criteria of MEN1. Conclusions A Chinese family with a new heterozygous mutation （1649_ 1650insC ） in the MEN1 gene, which was not reported previously, is herein described. With genetic screening, it is possible to diagnose the disease at an earlier stage.