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


BERTOLA F., FILOCAMO M., CASATI G., MORT M., ROSANO C., TYLKI-SZYMANSKA A., et al.

HUMAN MUTATION, cilt.32, 2011 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 32 Konu: 6
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1002/humu.21479
  • Dergi Adı: HUMAN MUTATION

Özet

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.