Article

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

Consortium for Human Molecular Genetics, Milano Bicocca University, Monza, Italy.
Human Mutation (Impact Factor: 5.05). 06/2011; 32(6):E2189-210. DOI: 10.1002/humu.21479
Source: PubMed

ABSTRACT 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.

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