塞尔维亚MEN1患者的新型突变：基因型-表型相关性

Novel Mutations in Serbian MEN1 Patients: Genotype-phenotype Correlation.

作者信息

Isailovic Tatjana, Milicevic Ivana, Macut Djuro, Petakov Milan, Ognjanovic Sanja, Popovic Bojana, Antic Ivana Bozic, Bogavac Tamara, Kovacevic Valentina Elezovic, Ilic Dusan, Damjanovic Svetozar

机构信息

Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.

Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia.

出版信息

J Med Biochem. 2019 Mar 1;38(1):38-44. doi: 10.2478/jomb-2018-0013. eCollection 2019 Mar.

DOI:10.2478/jomb-2018-0013

PMID:30820182

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6298455/

Abstract

BACKGROUND

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome characterized by the occurrence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA) and pancreatic neuroendocrine tumor (pNET). Whether the underlying mutations in gene predict clinical presentation of affected heterozygotes or not, is still a matter of a debate.

METHODS

Clinical and genetic analysis of 90 consecutive MEN1 patients was performed in a retrospective, single - center study.

RESULTS

mutation was found in 67 (74.4%) patients belonging to 31 different families. Twenty nine different heteozygous mutations were found, including 6 novel point mutations (W220G, 941delG, 1088del7, 1184insA, 1473del10, 1602del17) and one large deletion of exon 8. Truncating mutations predicted development of pNETs (OR=5.8, 95% CI 1.7 - 19.7%) and PHPT (OR=4.3, 95% CI 1.5 - 12.4%).

CONCLUSIONS

Large number of novel mutations among MEN1 patients confirmed previously reported data. PNETs and PHPT were more frequent in patients with truncating mutations.

摘要

背景

1型多发性内分泌腺瘤病（MEN1）是一种常染色体显性癌症综合征，其特征为原发性甲状旁腺功能亢进症（PHPT）、垂体腺瘤（PA）和胰腺神经内分泌肿瘤（pNET）的发生。该基因的潜在突变是否能预测受影响杂合子的临床表现仍存在争议。

方法

在一项回顾性单中心研究中，对90例连续的MEN1患者进行了临床和基因分析。

结果

在来自31个不同家庭的67例（74.4%）患者中发现了突变。发现了29种不同的杂合突变，包括6种新的点突变（W220G、941delG、1088del7、1184insA、1473del10、1602del17）和外显子8的一个大片段缺失。截短突变预测pNETs（比值比=5.8，95%可信区间1.7 - 19.7%）和PHPT（比值比=4.3，95%可信区间1.5 - 12.4%）的发生。