MEN1基因第9号内含子突变致多发性内分泌腺瘤病1型一例及其家系研究  

Intron 9 of MEN1 gene mutation-induced multiple endocrine neoplasia type 1 ： one case and analysis of his pedigree

作　　者：张慧[1] 李平[1] 桑剑锋[2] 陈骏[3] 王维敏[1] 黄洪[1] 胡云[1] 

机构地区：[1]南京大学医学院附属鼓楼医院内分泌科,210008 [2]南京大学医学院附属鼓楼医院普外科,210008 [3]南京大学医学院附属鼓楼医院病理科,210008

出　　处：《中华内分泌代谢杂志》2012年第4期311-314,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：南京市医学科技发展项目（ZKX10016）;国家自然科学基金青年基金（81000350）

摘　　要：研究1个多发性内分泌腺瘤1型（MEN1）家系的MEN1基因突变情况，并初步探讨该突变所导致疾病发生的可能机制。提取患者及其家系成员外周血及相关肿瘤组织基因组DNA，运用PCR扩增MENl基因外显子及其周边内含子区域，测序，亚克隆测序鉴定其杂合性。进一步免疫组化观察肿瘤组织中menin蛋白的表达。先证者及2个家系成员MEN1基因第9号内含子存在一种杂合缺失突变，IVS9＋1—11delGTGAGGGACAG。并首次证实先证者甲状旁腺肿瘤组织中menin蛋白表达缺失。MEN1基因第9号内含子起始处杂合缺失突变，IVS9＋1_11delGTGAGGGACAG，为新发现的中国人MEN1致病基因类型。该突变可能影响MEN1 mRNA的剪接，所合成的menin蛋白易降解及表达缺失，最终导致肿瘤发生。To study the MEN1 gene mutations in a multiple endocrine neoplasia type 1 （ MEN1 ） family, and determine the possible mechanism of disease induced by the mutations. Genomic DNA was isolated from peripheral blood leukocytes and the MENl-related tumor tissues of the patient and the family members, then the coding exons and exon/intron boundaries of the MEN1 gene were amplified by polymerase chain reaction （PCR） and sequenced. Subclone sequencing was performed to identify the heterozygosity. Further immunohistochemistry was performed to observe menin protein expression in the tumor tissues. We identified a heterozygous deletion mutation of intron 9 （ IVS9 ＋1_1 ldelGTGAGGGACAG） in the proband and two family members. We also demonstrated for the first time that the expression of menin protein is absent in the parathyroid adenoma tissue. The heterozygous mutation in the initial of intron 9, Ivsg＋ 1_11 delGTGAGGGACAG is a new type of MEN1 gene mutations in China. This mutation may produce an aberrant splicing of MEN1 mRNA, generating easily degradation and loss of expression of menin protein and resulting eventually in the disease.

关 键 词：多发性内分泌腺瘤病1型 MEN1基因 基因突变 MENIN蛋白 

分 类 号：R736[医药卫生—肿瘤]