CAJ | 학술논문

研究1个多发性内分泌腺瘤Ⅰ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J周血及相关肿瘤组织基因组DNA,运用PCR扩增MEN1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_11delGTGAGGGAC AG.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.
연구1개다발성내분비선류Ⅰ형( MEN1)가계적MEN1기인돌변정황,병초보탐토해돌변소도치질병발생적가능궤제.제취환자급기가계성원외J주혈급상관종류조직기인조DNA,운용PCR확증MEN1기인외현자급기주변내함자구역,측서,아극륭측서감정기잡합성.진일보면역조화관찰종류조직중menin단백적표체.선증자급2개가계성원MEN1기인제9호내함자존재일충잡합결실돌변,IVS9+1_11delGTGAGGGAC AG.병수차증실선증자갑상방선종류조직중menin단백표체결실.MEN1기인제9호내함자기시처잡합결실돌변,IVS9+1_11delGTGAGGGACAG,위신발현적중국인MEN1치병기인류형.해돌변가능영향MEN1 mRNA적전접,소합성적menin단백역강해급표체결실,최종도치종류발생.
To study the MEN1 gene mutations in a multiple endocrine neoplasia type 1 ( MEN 1 ) family,and determine the possible mechanism of disease induced by the mutations.Genomic DNA was isolated from peripheral blood leukocytes and the MEN1-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_11 delGTGAGGGACAG) in the proband and two family menbers.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,IVS9+ 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.