多发性内分泌腺瘤综合征家系MEN1基因突变及功能分析

目的对一例多发性内分泌腺瘤综合征（multiple endocrine neoplasia type1，MEN1）家系进行基因突变检测及功能分析，以探讨MEN1发病的分子机制。方法对家系两名确诊患者及其他6名成员进行相关生化检查，留取外周血液标本，提取基因组DNA，采用PCR方法扩增MEN1基因所有编码序列，包括9个外显子及外显子／内含子边界，并进行直接测序。免疫组织化学法对2名患者肿瘤组织menin蛋白进行检测。结果2名患者MEN1基因第三外显子存在插入突变C．433-434ins CTTC，可导致开放阅读框移位并提前出现终止密码子。家系其他成员未发现MEN1基因突变。患者肿瘤组织中无menin蛋白表达。结论一种新型的MEN1基因突变形式被定位，这将有利于MEN1疾病的早期分子诊断。

A novel mutation of MEN1 gene in a kindred of multiple endocrine neoplasia type 1 syndrome

Objective To investigate the mutation of multiple endocrine neoplasia type 1 （ MEN1 ） gene in a Chinese kindred of multiple endocrine neoplasis. Methods Two patients in this family were diagnosed as MEN1 by the typical clinical findings of parathyroidoma, insulinoma and pituitary adenoma. Peripheral blood samples were collected from 2 patients with MEN1 and 6 family members, DNA was extracted from blood samples. The coding sequences, including 9 coding exons and exon/ intron boundaries of the MEN1 gene, were amplified by polymerase chain reaction （PCR） and subjected to direct sequencing. Immunohistochernistry was used to detect the expression of menin protein in tumors. Results The sequence analysis showed a novel insert mutation in exon 3 in samples of 2 MEN1 patients, resulting in an open reading frames shift and produced an earlier stop codon; the mutation was not detected in 6 family members. Menin protein was not detected in those tumors.Conclusion A novel mutation of MEN1 gene in Chinese patients with MENI has been detected, and it would be useful for diagnosis of the disease.