Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing.
Eun-Hee ChoJae Woong MinSun Shim ChoiHoon Sung ChoiSang Wook KimPublished in: Endocrinology and metabolism (Seoul, Korea) (2017)
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.
Keyphrases
- type diabetes
- cardiovascular disease
- end stage renal disease
- glycemic control
- chronic kidney disease
- molecular docking
- ejection fraction
- randomized controlled trial
- risk factors
- prognostic factors
- gene expression
- clinical trial
- peritoneal dialysis
- metabolic syndrome
- adipose tissue
- insulin resistance
- small molecule
- current status
- dna methylation
- patient reported outcomes
- binding protein