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.
Hum Mutat
; 32(6): E2189-210, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21394825
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mucopolissacaridose I
/
Iduronidase
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Humans
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article