Neonatal and late-onset diabetes mellitus caused by failure of pancreatic development: report of 4 more cases and a review of the literature.
出版年：2022-11-22
期刊名称：Pediatrics
影响因子：胰腺不发育或发育不全
发布目录：Pediatrics 2008 Jun;121(6):e1541-7
疾病分类：胰腺发育障碍引发的新生儿永久性糖尿病
主题词：主要主题词：Diabetes Mellitus; Pancreas
文献摘要: 目的:目的 胰腺发育障碍引发的新生儿永久性糖尿病很罕见， 迄今仅报道了少数几种遗传病因。 本文报道了因胰腺不发育或发育不全所引起的4例新生儿永久性糖尿病患儿的临床及遗传学特征。
OBJECTIVE:Permanent neonatal diabetes mellitus caused by developmental failure of the pancreas is rare. Thus far, only a few genetic causes have been reported. We now report the clinical and genetic aspects of 4 more cases of permanent neonatal diabetes mellitus caused by pancreatic agenesis or hypoplasia.
患者与方法:研究对象和方法 4例患儿均来自近亲家系， 且均表现为糖尿病和胰腺外分泌功能不全。 计算机断层摄影扫描显示其中3例为胰腺不发育，1例为胰腺发育不良。 从患儿以及未受累的家庭成员的血样中提取DNA， 应用聚合酶链反应扩增特异性基因， 并对纯化产物进行DNA测序。
PATIENTS AND METHODS:All 4 of the patients were from consanguineous kinships, and all presented with diabetes mellitus and pancreatic exocrine insufficiency. Three patients had pancreatic agenesis, and 1 had pancreatic hypoplasia on computed tomography scan. DNA was extracted from blood samples of patients and unaffected family members. Specific genes were amplified by polymerase chain reaction and characterized by DNA sequencing.
结果:结果 编码转录因子的几个基因在胰腺发育中发挥着已知的作用， 我们对这些基因在受累患儿及其未受累家庭成员中所表现出来的特征进行了描述。 这些基因包括Pdx1基因 (该基因为胰腺发育及胰岛b细胞分化的主要调控因子) 以及在胰腺发育早期表达的其他转录因子， 即Ptf1a﹑ Sox9﹑ Sox17﹑ Hnf6和HlxB9基因。 从这些患儿中我们发现了数种新的基因多态性。 然而， 这些基因多态性在未受累的个体中也存在。 在所有这些基因中没有发现致病性基因突变。
RESULTS:Several genes that encode transcription factors that have known roles in pancreas development were characterized in the affected children and unaffected family members. These genes include Pdx1, the master regulator of pancreas development and beta-cell differentiation, and other transcription factors that are expressed early in pancreas development, namely, Ptf1a, Sox9, Sox17, Hnf6, and HlxB9. Several novel polymorphisms were found in our patients. However, these were also present in unaffected individuals. No disease-causing mutations were found in any of these genes.
结论:结论 从本文所报道的4例患儿中获得的这些发现加入文献已报道的4例之中， 文献所报道的4例胰腺不发育或发育不全患儿中Pdx1结构基因正常。 除Pdx1基因上游启动子元件外， 本次分析还扩展筛查了其他4个候选基因。 4例患儿中有2例为同胞， 2例为孤立病例， 因此本次报道的病例可能属于不同病因。
CONCLUSIONS:These findings add to the 4 cases already in the literature in which the Pdx1 structural gene has been found to be normal in patients with pancreatic agenesis or hypoplasia. The analysis here has been extended to include the screening of 4 other candidate genes in addition to promoter elements upstream of the Pdx1. Two of the cases occurred in a sibling pair, and 2 were isolated, so there may be more than 1 etiology in the cases reported here.
