Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing

Eun Hee Cho; Jae Woong Min; Sun Shim Choi; Hoon Sung Choi; Sang Wook Kim

doi:10.3803/EnM.2017.32.2.296

Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing

Endocrinol Metab (Seoul). 2017 Jun;32(2):296-301. doi: 10.3803/EnM.2017.32.2.296. Epub 2017 May 29.

Authors

Eun Hee Cho¹, Jae Woong Min², Sun Shim Choi², Hoon Sung Choi¹, Sang Wook Kim³

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
² Department of Medical Biotechnology, Institute of Bioscience and Biotechnology, Kangwon National University College of Biomedical Science, Chuncheon, Korea.
³ Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea. sangwookkim@kangwon.ac.kr.

Abstract

Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.

Keywords: Computational biology; Glucokinase; Maturity-onset diabetes of the young.