Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter Microdeletion Including IRS2.
Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter Microdeletion Including IRS2.
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DOI：
10.1210/js.2018-00175
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发表时间：
2018-10-01
影响因子：
4.1
通讯作者：
Ikegami H
中科院分区：
文献类型：
--
作者：
Babaya N;Noso S;Hiromine Y;Ito H;Taketomo Y;Yamamoto T;Kawabata Y;Ikegami H
糖尿病是一种由环境和遗传因素复杂相互作用引起的多因素疾病。然而，一些糖尿病病例是由有限数量的突变基因引起的。染色体13 q缺失综合征是一种极为罕见的遗传性疾病，由染色体13 q区域的结构和功能单体性引起。我们报告的情况下，一个38岁的日本男子与Chr13 q缺失（嵌合模式与杂合子环Chr13 q）谁开发糖尿病。早发性糖尿病的发展，在这个病人，因为胰岛素抵抗和缺乏足够的胰岛素分泌。微阵列分析确定了一个4.8 Mb的远端Chr13 q缺失，导致40个基因的拷贝数丢失。在这些基因中，胰岛素受体底物2基因（IRS2）是该患者发生糖尿病的最可能的致病候选基因，基于IRS2敲除小鼠模型，其具有与人类糖尿病表型非常相似的异常葡萄糖和胰岛素稳态。这些数据提供了重要的信息，包括在IRS2中的Chr13 q微缺失对人类糖尿病发病机制的贡献。
Diabetes mellitus is a multifactorial disease caused by a complex interaction of environmental and genetic factors. Some diabetes mellitus cases, however, are caused by a limited number of mutant genes. Chromosome 13q deletion syndrome, an extremely rare genetic disorder, is caused by structural and functional monosomy of the 13q chromosomal region. We report the case of a 38-year-old Japanese man with Chr13q deletion (a mosaic pattern with heterozygous ring Chr13q) who developed diabetes mellitus. Early-onset diabetes mellitus developed in this patient because of insulin resistance and a lack of adequate insulin secretion. Microarray analysis identified a 4.8-Mb deletion of distal Chr13q, leading to a copy number loss of 40 genes. Among those genes, the insulin receptor substrate 2 gene (IRS2) was the most likely causative candidate for the development of diabetes mellitus in this patient, based on the model of IRS2 knockout mice, which have abnormal glucose and insulin homeostasis closely resembling the human diabetes phenotype. These data provide important information regarding the contribution of a microdeletion of Chr13q, including in IRS2, to the pathogenesis of diabetes mellitus in humans.