Abstract

In the era of precision medicine, the tremendous progress in next-generation sequencing technologies has allowed the identification of an ever-increasing number of genes associated with known Mendelian disorders. Neonatal diabetes mellitus is a rare, genetically heterogeneous endocrine disorder diagnosed before 6 months of age. It may occur alone or in the context of genetic syndromes. Neonatal diabetes mellitus has been linked with genetic defects in at least 26 genes to date. Novel mutations in these disease-causing genes are being reported, giving us a better knowledge of the molecular events that occur upon insulin biosynthesis and secretion from the pancreatic β-cell. Of great importance, some of the identified genes encode proteins that can be therapeutically targeted by drugs per os, leading to transitioning from insulin to sulfonylureas. In this review, we provide an overview of pancreatic β-cell physiology, present the clinical manifestations and the genetic causes of the different forms of neonatal diabetes, and discuss the application of next-generation sequencing methods in the diagnosis and therapeutic management of neonatal diabetes and on research in this area.

摘要

在精密医学时代，下一代测序技术的巨大进步已使人们能够鉴定出与已知孟德尔疾病有关的基因，数量在不断增加。新生儿糖尿病是一种罕见的，遗传异质性内分泌疾病，在6个月大之前就被诊断出。它可以单独发生，也可以在遗传综合症的背景下发生。迄今为止，新生儿糖尿病已与至少26个基因的遗传缺陷相关。这些致病基因中的新突变得到了报道，使我们对胰岛素生物合成和胰腺β细胞分泌后发生的分子事件有了更好的了解。极为重要的是，某些已识别的基因编码的蛋白质可以被药物以口服方式治疗。，导致从胰岛素向磺酰脲过渡。在这篇综述中，我们提供了胰腺β细胞生理学概述，介绍了各种形式的新生儿糖尿病的临床表现和遗传原因，并讨论了下一代测序方法在新生儿糖尿病的诊断和治疗管理中的应用以及该领域的研究。