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. © 2011 Wiley-Liss, Inc.
Bertola, F., Filocamo, M., Casati, G., Mort, M., Rosano, C., Tylki-Szymanska, A., et al. (2011). IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. HUMAN MUTATION, 32(6), E2189-E2210 [10.1002/humu.21479].
Citazione: | Bertola, F., Filocamo, M., Casati, G., Mort, M., Rosano, C., Tylki-Szymanska, A., et al. (2011). IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. HUMAN MUTATION, 32(6), E2189-E2210 [10.1002/humu.21479]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles | |
Autori: | Bertola, F; Filocamo, M; Casati, G; Mort, M; Rosano, C; Tylki-Szymanska, A; Tüysüz, B; Gabrielli, O; Grossi, S; Scarpa, M; Parenti, G; Antuzzi, D; Dalmau, J; Rocco, MD; Vici, CD; Okur I; Rosell, J; Rovelli, A; Furlan, F; Rigoldi, M; Biondi, A; Cooper, DN; Parini, R | |
Autori: | ||
Data di pubblicazione: | 2011 | |
Lingua: | English | |
Rivista: | HUMAN MUTATION | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1002/humu.21479 | |
Appare nelle tipologie: | 01 - Articolo su rivista |