title: Evaluation and identification of IDUA gene mutations in Turkishpatients with mucopolysaccharidosis type I.
abstract: OBJECTIVE
  This study aimed to identify IDUA gene mutations in Turkish patients morphologically (phenotypic) diagnosed with MPS type I. It also sought to discuss the possible effects of detected mutations on alpha-L-iduronidase enzyme function based on current knowledge.
  
  
  METHODS
  Genetic analysis was carried out in 15 patients using direct DNA sequencing. Moreover, segregation analysis was performed among family members to predict the pathogenic effect of novel mutations, and computational programs were used to predict their functional impact.
  
  
  RESULTS
  Nine different mutations (c.494-1G>A, c.793-6C>G, c.793-5C>A, p.M1L, p.Y64X, p.A327P, p.W402X, p.P533L, and p.R628X) were identified. Computational analysis results supported the pathogenicity of novel mutations, suggesting improper splicing. Seven already-known polymorphisms were detected in the screened cohort as well.
  
  
  CONCLUSIONS
  Our results revealed heterogeneity in the mutation spectrum of Turkish patients. Six of the mutations, including the novel ones, have never before been reported in the Turkish population. Moreover, 5 patients who were phenotypically diagnosed with MPS type I could not be confirmed by genetic analysis, indicating the importance of the molecular characterization of MPS subtypes.
authors: Department of Biology, Faculty of Science and Arts, Aksaray University, Aksaray, Turkey.
authors: Nazente
authors: N
authors: Atçeken
authors: Institute of Child Health, Hacettepe University, Ankara, Turkey.
authors: Rıza Köksal
authors: RK
authors: Özgül
authors: Department of Pediatrics, Metabolism Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Didem
authors: D
authors: Yücel Yilmaz
authors: Department of Pediatrics, Metabolism Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Ayşegül
authors: A
authors: Tokatli
authors: Department of Pediatrics, Metabolism Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Turgay
authors: T
authors: Coşkun
authors: Department of Pediatrics, Metabolism Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Hatice Serap
authors: HS
authors: Sivri
authors: Department of Pediatrics, Metabolism Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Ali
authors: A
authors: Dursun
authors: Department of Biology, Faculty of Science and Arts, Aksaray University, Aksaray, Turkey.
authors: Mehmet
authors: M
authors: Karaca
mesh_terms: D005820:Genetic Testing; D006801:Humans; D007068:Iduronidase; D008059:Mucopolysaccharidosis I; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: C000615655:IDUA protein, human; D007068:Iduronidase
keywords: IDUA gene; MPS type I; alpha-L-iduronidase; mutation analysis