Mutations in the iduronate-2-sulfatase gene in 12 Spanish patients with hunter disease

Gort, Laura; Coll, María Josep; Chabás, Amparo

doi:10.1002/humu.1380110123

Cited by 5 publications

(6 citation statements)

References 18 publications

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“…All four of these point mutations were novel. A nonsense mutation identified in the present study in exon IX (R443X) in patient U154 has been reported previously (Sukegawa et al, 1992;Bunge et al, 1992; Froissart et al, 1993;Rathmann et al, 1996;Gort et al, 1998) Missense mutations were detected in three patients: U129 (Y264N); U20 (Q465P, polar→ nonpolar); and U42 (R468W -hydrophilicƒhydrophobic). While the mutations in U129 and U20 are novel, the R468W change in patient U42 is a relatively common mutation (Crotty et al, 1992;Hopwood et al, 1993; Whitley et al, 1993;Schröder et al, 1994;Li et al, 1995;Popowska et al, 1995;Goldenfum et al, 1996;Lissens et al, 1997;Villani et al, 1997;Isogai et al, 1998).…”

supporting

confidence: 56%

“…This indicates that the altered residues may be in some way essential to the function or structure of IDS. However, as the promoter region has not yet been analyzed in these samples, a more fundamental cause of the disease cannot be ruled out.The 1246C→T mutation has also been previously reported (Bunge et al, 1992;Flomen et al, 1992;Lissens et al, 1997;Goldenfum et al, 1996;Rathmann et al, 1996;Gort et al, 1998). This single base substitution (AGGC→AGgt) in exon VIII creates an alternate donor splice site at codon 374, thus effectively resulting in a 60bp deletion (Flomen et al, 1992).…”

mentioning

confidence: 64%

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Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: Characterisation of 6 novel mutations

1999

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supporting

confidence: 56%

mentioning

confidence: 64%

Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: Characterisation of 6 novel mutations

1999

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“…In addition to these missense mutations, a unique point mutation, c.1122C>T (G374G), has been found in many other ethnicities, European countries, Russia, and Korea (Bunge et al 1993;Rathmann et al 1996;Gort et al 1998;Balzano et al 1998;Vafiadaki et al 1998;Karsten et al 1998;Hartog et al 1999;Filocamo et al 2001). This common mutation appears to relate mainly to the attenuated phenotype, as indicated in our structural analysis, but some patients showed severe manifestations.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the mutation A85T is widely found in the world, but there has been no clear phenotype/genotype relationship (Rathmann et al 1996;Gort et al 1998;Froissart et al 1998;Li et al 1999). Reasons for the discrepancy would be partly due to the manner of classifying the severity of Hunter disease.…”

Section: Discussionmentioning

confidence: 99%

“…Ten fragments of the I2S gene, exons and exon/intron boundaries, were amplified by polymerase chain reaction (PCR) using primers listed in Table 2 (Bunge et al 1993;Rathmann et al 1996;Isogai et al 1998;Gort et al 1998). The PCR reaction was carried out in a total volume of 50 ll containing 1.25 units of ExTaq polymerase, 10 nmol dNTPs, genomic DNA (100 ng), and Liver size on physical examination f I2S activity enzymatic activity of iduronate-2-sulfatase g nd not detectable; detection limit of the experiment was 1.6 nmol/mg protein/4 h; normal range 58.4-114 nmol/mg protein/4 h the respective primers (0.5-2.0 lM).…”

Section: Dna Preparation and Sequencingmentioning

confidence: 99%

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Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II

Kato

Kuratsubo

et al. 2005

J Hum Genet

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We investigated mutations of the iduronate-2-sulfatase (I2S) gene and structural characteristics of I2S to clarify genotype/phenotype relationships in 18 Japanese patients with mucopolysaccharidosis type II. The I2S gene was analyzed in five patients with a severe phenotype and in 13 patients with an attenuated phenotype. The tertiary structural model of the human I2S was constructed by homology modeling using the arylsulfatase structure as a template. We identified four missense mutations and a nonsense mutation in the severe phenotype; four missense, two nonsense, three frame shifts, and one each of splice and amino acid deletion in the attenuated phenotype. Seven of them (L73del, Q75X, G140R, C171R, V401 fs, C422 fs, and H441 fs) were novel mutations. Structural analysis indicated that the residues of the mutations found in the severe phenotype would have direct interactions with the active site residues or should break the hydrophobic core domain of I2S, whereas residues of the missense mutations found in the attenuated phenotype were located in the peripheral region. In addition, effects by deletion or frameshift mutations could also be interpreted by the structure. Structural analysis of mutant proteins would help in understanding the genotype/phenotype relationships of Hunter disease.

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Molecular analysis of 40 Italian patients with mucopolysaccharidosis type II: New mutations in the iduronate-2-sulfatase (IDS) gene

et al. 2001

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Mucopolysaccharidosis type II (MPS2, or Hunter syndrome), rare X-linked lysosomal storage disorder, results from deleterious mutations in the iduronate-2-sulfatase (IDS) gene. We report here the mutational analysis of a total of 40 unrelated Italian MPS II patients ranging from mild to severe phenotype. We are able to assign the genotype to 29 of them (72.5%), identifying 22 different mutations, five of which are unpublished (c.533delTT, W12X, N265I, c.1131-1142del, c.1131-1305del). A total of 55.2% of the molecularly characterised patients resulted from missense mutations, 20.7% from nonsense mutations, and another 13.8% of patients from small deletions (<20pb) or splice mutations, whereas 10.3% of the cases carried major structural alterations such as large deletion and rearrangements. The results reported here support the evidence of the mutational heterogeneity of the IDS gene as well as the difficulty to correlate genotype and phenotype in the patients with MPSII. However, the molecular characterisation of the patients is advantageous, making the carrier detection feasible for the females in the family at risk and improving the reliability of prenatal diagnosis techniques. Moreover, it provides a good foundation for therapeutic strategies.

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Mutations in the iduronate-2-sulfatase gene in 12 Spanish patients with hunter disease

Cited by 5 publications

References 18 publications

Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: Characterisation of 6 novel mutations

Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: Characterisation of 6 novel mutations

Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II

Molecular analysis of 40 Italian patients with mucopolysaccharidosis type II: New mutations in the iduronate-2-sulfatase (IDS) gene

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