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Research Article: Pathogenic monoallelic variants in GLIS3 increase type 2 diabetes risk and identify a subgroup of patients sensitive to sulfonylureas

Date Published: 2023-12-05

Abstract:
GLIS3 encodes a transcription factor involved in pancreatic beta cell development and function. Rare pathogenic, bi-allelic mutations in GLIS3 cause syndromic neonatal diabetes whereas frequent SNPs at this locus associate with common type 2 diabetes risk. Because rare, functional variants located in other susceptibility genes for type 2 diabetes have already been shown to strongly increase individual risk for common type 2 diabetes, we aimed to investigate the contribution of rare pathogenic GLIS3 variants to type 2 diabetes.

Introduction:
Type 2 diabetes, like many other multifactorial disorders, includes monogenic forms that are rare, more severe, and appear earlier in life than common polygenic forms [1]. Rare, pathogenic, bi-allelic variants in GLIS3 cause a severe syndrome that includes neonatal diabetes [2]. GLIS family zinc finger 3 (GLIS3) is a transcription factor playing a major role in pancreatic beta cell development and function. Notably, it enhances the transcription of INS by binding to its promoter and recruiting the transcription…

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