title: Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing.
abstract: OBJECTIVE
  To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship.
  
  
  METHODS
  Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses.
  
  
  RESULTS
  A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B, HNF1A, PDX1, and BLK mutations in the others. We identified five novel missense mutations - three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic.
  
  
  CONCLUSIONS
  The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Anık
authors.forename: Gönül
authors.initials: G
authors.lastname: Çatlı
authors.forename: Ayhan
authors.initials: A
authors.lastname: Abacı
authors.forename: Erkan
authors.initials: E
authors.lastname: Sarı
authors.forename: Ediz
authors.initials: E
authors.lastname: Yeşilkaya
authors.forename: Hüseyin Anıl
authors.initials: HA
authors.lastname: Korkmaz
authors.forename: Korcan
authors.initials: K
authors.lastname: Demir
authors.forename: Ayça
authors.initials: A
authors.lastname: Altıncık
authors.forename: Hale Ünver
authors.initials: HÜ
authors.lastname: Tuhan
authors.forename: Sefa
authors.initials: S
authors.lastname: Kızıldağ
authors.forename: Behzat
authors.initials: B
authors.lastname: Özkan
authors.forename: Serdar
authors.initials: S
authors.lastname: Ceylaner
authors.forename: Ece
authors.initials: E
authors.lastname: Böber
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense; D010641:Phenotype; D014421:Turkey; D055815:Young Adult
chemical_list: D005941:Glucokinase