IDUA Mutational Profiling of a Cohort of 102 European Patients with Mucopolysaccharidosis Type I: Identification and Characterization of 35 Novel alpha-L-iduronidase (IDUA) Alleles

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Bertola F., Filocamo M., Casati G., Mort M., Rosano C., Tylki-Szymanska A., ...More

HUMAN MUTATION, vol.32, no.6, 2011 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 32 Issue: 6
  • Publication Date: 2011
  • Doi Number: 10.1002/humu.21479
  • Journal Name: HUMAN MUTATION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: IDUA, mucoplysaccharidosis type I, Hurler disease, genotype-phenotype analysis, molecular modelling, MutPred analysis, in vitro splicing analysis, AMINO-ACID SUBSTITUTIONS, MOLECULAR-GENETICS, MISSENSE MUTATIONS, HUMAN-DISEASE, NOMENCLATURE, EXPRESSION, FREQUENCY, FAMILIES, HURLER, MODEL
  • Gazi University Affiliated: Yes


Mutational analysis of the IDUA gene was performed in a cohort of 102 European patients with mucopolysaccharidosis type I. A total of 54 distinct mutant IDUA alleles were identified, 34 of which were novel including 12 missense mutations, 2 nonsense mutations, 12 splicing mutations, 5 micro-deletions, 1 micro-duplication 1 translational initiation site mutation, and 1 'no-stop' change (p.X654RextX62). Evidence for the pathological significance of all novel mutations identified was sought by means of a range of methodological approaches, including the assessment of evolutionary conservation, RT-PCR/in vitro splicing analysis, MutPred analysis and visual inspection of the 3D-model of the IDUA protein. Taken together, these data not only demonstrate the remarkable mutational heterogeneity characterizing type 1 mucopolysaccharidosis but also illustrate our increasing ability to make deductions pertaining to the genotype-phenotype relationship in disorders manifesting a high degree of allelic heterogeneity. (C) 2011 Wiley-Liss, Inc.