title: Identification of Candidate Gene Variants in Korean MODY Families by Whole-Exome Sequencing.
abstract: OBJECTIVE
  To date, 13 genes causing maturity-onset diabetes of the young (MODY) have been identified. However, there is a big discrepancy in the genetic locus between Asian and Caucasian patients with MODY. Thus, we conducted whole-exome sequencing in Korean MODY families to identify causative gene variants.
  
  
  METHODS
  Six MODY probands and their family members were included. Variants in the dbSNP135 and TIARA databases for Koreans and the variants with minor allele frequencies >0.5% of the 1000 Genomes database were excluded. We selected only the functional variants (gain of stop codon, frameshifts and nonsynonymous single-nucleotide variants) and conducted a case-control comparison in the family members. The selected variants were scanned for the previously introduced gene set implicated in glucose metabolism.
  
  
  RESULTS
  Three variants c.620C>T:p.Thr207Ile in PTPRD, c.559C>G:p.Gln187Glu in SYT9, and c.1526T>G:p.Val509Gly in WFS1 were respectively identified in 3 families. We could not find any disease-causative alleles of known MODY 1-13 genes. Based on the predictive program, Thr207Ile in PTPRD was considered pathogenic.
  
  
  CONCLUSIONS
  Whole-exome sequencing is a valuable method for the genetic diagnosis of MODY. Further evaluation is necessary about the role of PTPRD, SYT9 and WFS1 in normal insulin release from pancreatic beta cells.
authors.affiliation: Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ye Jee
authors.initials: YJ
authors.lastname: Shim
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Su-Kyeong
authors.initials: SK
authors.lastname: Hwang
authors.forename: Bong Seok
authors.initials: BS
authors.lastname: Choi
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Choi
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Cho
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Jang
authors.forename: Cheol Woo
authors.initials: CW
authors.lastname: Ko
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D059472:Exome; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea