Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

Matte, Úrsula da Silveira; Yogalingam, Gouri; Brooks, Doug A.; Leistner, Sandra; Schwartz, Ida Vanessa Döederlein; Lima, Luciane Cauduro; Norato, Denise Yvonne Janovitz; Brum, Jaime Moritz; Beesley, Clare E.; Winchester, Bryan; Giugliani, Roberto; Hopwood, John J.

doi:10.1016/s1096-7192(02)00200-7

Cited by 78 publications

(56 citation statements)

References 19 publications

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“…php?ID=12), our data aligns with the literature for MPS I, showing the most frequent mutations are W402X and P533R (20) and presence of both alleles is linked to a severe phenotype of the disease. Genotypic determination may be useful in providing individual parameters of the patient's therapeutic response to therapies such as ERT and BMT as well.…”

Section: Discussionsupporting

confidence: 89%

Mucopolysaccharidosis type I, II and VI and response to enzyme replacement therapy: Results from a single-center case series study

Franco

Dib

Agarwal

et al. 2017

IRDR

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Section: Discussionsupporting

confidence: 89%

Mucopolysaccharidosis type I, II and VI and response to enzyme replacement therapy: Results from a single-center case series study

Franco

Dib

Agarwal

et al. 2017

IRDR

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“…for England (11,12), 5.6% for Italy (15), 2.2% for Austria (22), and 3.3%-8.3% for Brazil (16,23). It is worth noting that the studies were performed mostly on European Caucasians and that the frequency of this mutation was 3.5% for Turkish MPS-I patients (24).…”

Section: Discussionmentioning

confidence: 99%

Evaluation and identification of IDUA gene mutations in Turkishpatients with mucopolysaccharidosis type I

Atçeken¹,

Özgül²,

Yılmaz³

et al. 2016

Turk J Med Sci

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Background/aim: This study aimed to identify IDUA gene mutations in Turkish patients morphologically (phenotypic) diagnosed with MPS type I. It also sought to discuss the possible effects of detected mutations on alpha-L-iduronidase enzyme function based on current knowledge.Materials and methods: Genetic analysis was carried out in 15 patients using direct DNA sequencing. Moreover, segregation analysis was performed among family members to predict the pathogenic effect of novel mutations, and computational programs were used to predict their functional impact.Results: Nine different mutations (c.494-1G>A, c.793-6C>G, c.793-5C>A, p.M1L, p.Y64X, p.A327P, p.W402X, p.P533L, and p.R628X) were identified. Computational analysis results supported the pathogenicity of novel mutations, suggesting improper splicing. Seven already-known polymorphisms were detected in the screened cohort as well. Conclusion:Our results revealed heterogeneity in the mutation spectrum of Turkish patients. Six of the mutations, including the novel ones, have never before been reported in the Turkish population. Moreover, 5 patients who were phenotypically diagnosed with MPS type I could not be confirmed by genetic analysis, indicating the importance of the molecular characterization of MPS subtypes.

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“…For these cases, clinical and biochemical investigations had been performed in detail (Brooks et al 2001;Beesley et al 2001;Matte et al 2003). The analysis was based on the distances between the wild type and mutant to determine the influence of the amino acid substitutions geographically and semiquantitatively according to the method previously described (Matsuzawa et al 2005).…”

Section: Color Imaging Of the Atoms Influenced By Representative Aminmentioning

confidence: 99%

Structural study on mutant α-l-iduronidases: insight into mucopolysaccharidosis type I

et al. 2008

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To elucidate the basis of mucopolysaccharidosis type I (MPS I), we constructed structural models of mutant a-L-iduronidases (IDUAs) resulting from 33 amino acid substitutions that lead to MPS I (17 severe, eight intermediate, and eight attenuated). Then, we examined the structural changes in the enzyme protein by calculating the number of atoms affected and determined the root-meansquare distance (RMSD) and the solvent-accessible surface area (ASA). In the severe MPS I group, the number of atoms influenced by a mutation and the average RMSD value were larger than those in the attenuated group, and the residues associated with the mutations identified in the severe group tended to be less solvent accessible than those in the attenuated group. The clinically intermediate phenotype group exhibited intermediate values for the numbers of atoms affected, RMSD, and ASA between those in the severe group and those in the attenuated group. The results indicated that large structural changes had occurred in the core region in the severe MPS I group and small ones on the molecular surface in the attenuated MPS I group. Color imaging revealed the distributions and degrees of the structural changes caused by representative mutations for MPS I. Thus, structural analysis is useful for elucidating the basis of MPS I. As there was a difference in IDUA structural change between the severe MPS I group and the attenuated one, except for a couple of mutations, structural analysis can help predict the clinical outcome of the disease.

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Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

Cited by 78 publications

References 19 publications

Mucopolysaccharidosis type I, II and VI and response to enzyme replacement therapy: Results from a single-center case series study

Mucopolysaccharidosis type I, II and VI and response to enzyme replacement therapy: Results from a single-center case series study

Evaluation and identification of IDUA gene mutations in Turkishpatients with mucopolysaccharidosis type I

Structural study on mutant α-l-iduronidases: insight into mucopolysaccharidosis type I

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