多发性内分泌肿瘤1型6例及其家系研究

Multiple endocrine neoplasia type 1 :six cases and analysis of their pedigrees

目的:分析6例多发性内分泌肿瘤1型(MEN1)患者及其家系成员的临床特点,研究MEN1基因突变特征。方法:收集患者及家系成员的临床资料,提取6例患者及其各自家系成员(共13例)外周血DNA,对MEN1基因编码区9个外显子进行PCR扩增,产物直接测序。结果:家系1中2例患者和2例家系成员MEN1基因第10外显子存在杂合突变c.1378C>T,家系2中1例患者MEN1基因第2外显子存在杂合突变c.80C>G,家系3中先证者及其母亲MEN1基因第9外显子存在杂合突变c.1225T>C,其余人员均未发现突变。其中MEN1基因突变c.80C>G和c.1225T>C为新发现的突变类型,c.1378C>T为已知突变类型。结论:MEN1基因突变分析有助于MEN 1患者早期诊断及其亲属的筛查。本研究发现2种新的MEN1突变类型能增加研究者对于MEN1遗传学特征的认识。

Objective：To analyze the clinical characters of six patients of multiple endocrine neoplasia type 1（MEN1）and their family members and investigate the features of MEN1 gene mutation in these families. Methods：Clinical data of MEN1 patients and their family members was collected. Genomic DNA was extracted from peripheral blood of six patients and their respective family members（thirteen in total）,then the 9 exons in coding sequences of MEN1 gene was amplified by PCR and subjected to direct sequencing. Results：We detected a heterozygous mutation within exon 10（c.1378CT）in two patients and two relatives in pedigree 1,a heterozygous mutation within exon 2（c.80CG）in one of patients in pedigree 2 and a heterozygous mutation within exon 9（c.1225TC）in the proband and her mother in pedigree 3,respectively. No mutation was found in other patients or relatives. The detected c.80CG and c.1225TC were two novel types of MEN1 mutation,while the mutation of c.1378 C T in MEN1 gene was already known.Conclusion：Analysis of MEN1 gene mutation contributes to early diagnosis of MEN1 patients and screening of family members. The two novel types of MEN1 gene mutation in this study may increase our knowledge concerning genetic feature of MEN1.