title: A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I.
abstract: OBJECTIVE
  To characterize the pathogenic mutations causing mucopolysaccharidosis type I (MPS I) in two Thai patients: one with Hurler syndrome (MPS IH), the most severe form, and the other with Scheie syndrome (MPS IS), the mildest. Both presented with distinctive phenotype including corneal clouding.
  
  
  METHODS
  The entire coding regions of the α-L-iduronidase (IDUA) gene were amplified by PCR and sequenced. Functional characterization of the mutant IDUA was determined by transient transfection of the construct into COS-7 cells.
  
  
  RESULTS
  Mutation analyses revealed that the MPS IH patient was homozygous for a previously reported mutation, c.252insC, while the MPS IS patient was found to harbor a novel c.826G>A (p.E276K) mutation. The novel p.E276K mutation was not detected in 100 unaffected ethnic-matched control chromosomes. In addition, the glutamic acid residue at codon 276 was located at a well conserved residue. Transient transfection of the p.E276K construct revealed a significant reduction of IDUA activity compared to that of the wild-type IDUA suggesting it as a disease-causing mutation.
  
  
  CONCLUSIONS
  This study reports a novel mutation, expanding the mutational spectrum for MPS I.
authors.affiliation: 1Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Korrakot
authors.initials: K
authors.lastname: Prommajan
authors.forename: Surasawadee
authors.initials: S
authors.lastname: Ausavarat
authors.forename: Chalurmpon
authors.initials: C
authors.lastname: Srichomthong
authors.forename: Vilavun
authors.initials: V
authors.lastname: Puangsricharern
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D020022:Genetic Predisposition to Disease; D006801:Humans; D007068:Iduronidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D008059:Mucopolysaccharidosis I / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D007068:Iduronidase