Endocrinol Metab.  2017 Jun;32(2):296-301. 10.3803/EnM.2017.32.2.296.

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

• Cho EH
• Min JW
• Choi SS
• Choi HS
• Kim SW

• KMID: 2384090
• DOI: http://doi.org/10.3803/EnM.2017.32.2.296

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.

Keyword

Glucokinase; Maturity-onset diabetes of the young; Computational biology

MeSH Terms

Computational Biology
Computer Simulation
Diabetes Complications
Diabetes Mellitus, Type 2*
Diagnosis
Glucokinase*
Humans
Glucokinase

Figure

• 

  Fig. 1 (A, B) Pedigrees of families harboring glucokinase (GCK) missense variants. Filled and empty symbols represent diabetic and non-diabetic individuals, respectively. Arrows indicate probands.

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  Fig. 2 Confirmation of the heterozygote missense mutation (c.92T>C, p.Leu30Pro) identified in the proband of family 1 by Sanger sequencing.

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