Center for Identification and Study of Individuals with Atypical Diabetes Mellitus

项目摘要-概述 摘要 在这里，我们描述了我们对国家非典型肺炎患者识别和研究中心的愿景 糖尿病对RFA-DK-17-006的反应。该中心的目的是召集主要的糖尿病中心 在糖尿病的临床评估、遗传学和生理学研究方面具有专业知识 在全国范围内呼吁患有非典型糖尿病的受试者设计： A)促进对原因不明的罕见/非典型糖尿病患者的研究； B)确定和分析表型和遗传型缺陷，这些缺陷可提供对更常见的、 普通人群中的异质性2型糖尿病(T2 DM)；以及 C)开发社区资源，通过数据库推动这一领域的研究，以促进 通过生物库样本和生计收集和传播表型和遗传数据 供糖尿病研究社区访问的生物库。 我们的中心假设是，对罕见/非典型形式的新病例的识别和研究 糖尿病将使人们对T2 DM的病因和遗传异质性有更深入的了解。 该中心以参与团体在过去三十年的往绩为基础，将 支持主要研究工作，以： I.建立在我们现有的单基因糖尿病资源、遗传学专业知识和对 糖尿病生物学开发和实施流程(基于系谱分析和战略 全外显子组测序)，用于识别和研究罕见和 无特征性形式的糖尿病； 二、创建一个全国性的合作者网络，以帮助确定并初步确定 已鉴定的家系； 三、采用我们现有的基于RedCap的单基因糖尿病数据库来创建和管理一项研究 罕见/非典型糖尿病数据库，活生生的生物库和生物质谱库，以及公共 供糖尿病研究界在未来研究中使用的门户网站；以及 四、通过提供对生物库的访问，促进未来对遗传变异影响的研究 材料和活生物库。 对这些人及其家人进行详细的表型、基因分型和基因测序将有助于 描述在普通人群中出现的罕见的非典型2型糖尿病亚型，并揭示 糖尿病发病机制的新途径。了解这些路径和它们的 组成分子应该指向治疗和/或预防T2 DM的新策略。

PROJECT SUMMARY – OVERVIEW ABSTRACT Here we describe our vision for the National Center for the Identification and Study of Individuals with Atypical Diabetes Mellitus in response to RFA-DK-17-006. The Center’s purpose is to convene key diabetes centers with expertise in the clinical assessment, genetics, and physiological study of diabetes as institutional foci of a nation-wide call for subjects with atypical forms of diabetes designed to: a) Foster the study of individuals with rare/atypical forms of diabetes mellitus of unknown cause; b) Identify and analyze phenotypic and genotypic defects that may provide insights into more common, heterogeneous forms of type 2 diabetes mellitus (T2DM) in the general population; and c) Develop a community resource to advance research in this area through a database to facilitate the collection and dissemination of phenotypic and genetic data with biorepository samples and a living biobank for access by the diabetes research community. Our central hypothesis is that the identification and study of new cases of rare/atypical forms of diabetes will yield greater insights into the etiology and genetic heterogeneity of T2DM. The Center, building on the track records of the participating groups over the last three decades, will support primary research endeavors to: i. Build on our existing monogenic diabetes resources, genetics expertise, and deep knowledge of the biology of diabetes to develop and implement processes (based on pedigree analysis and strategic whole exome sequencing) for identifying and studying individuals/families with rare and uncharacterized forms of diabetes; ii. Create a national network of collaborators to help ascertain and initially phenotype the individuals in pedigrees identified; iii. Adapt our existing REDCap-based monogenic diabetes database to create and manage a study database for rare/atypical forms of diabetes, a living biobank and biospecimen repository, and a public portal for use by the diabetes research community in future studies; and iv. Facilitate future investigation of the impact of genetic variation by providing access to biobanked materials and the living biobank. Detailed phenotyping, genotyping, and gene sequencing of these individuals and their families will help to characterize rare atypical subtypes present in the spectrum of T2DM in the general population, and reveal novel mechanistic pathways involved in the pathogenesis of diabetes. Knowledge of the pathways and their constituent molecules should point to novel strategies for the treatment and/or prevention of T2DM.