Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Hunter syndrome or mucopolysaccharidoses type II (MPS-II), is a lysosomal storage disorder caused by a deficiency in the activity of the enzyme iduronate-2-sulphatase (IDS). We have investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS-II patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations of the IDS gene were found in DNA from 9 patients two of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoint of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constitute major rearrangements of the gene. Interestingly, six of these rearrangements showed similar or identical patterns by Southern analysis suggestive for a region prone to structural alterations within the IDS gene. We also demonstrate the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. A contiguous gene deletion syndrome characterized by Hunter syndrome and epilepsy is also discussed.
Hum Mol Genet 1992 Jun
PMID:Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene. 130 77

Iduronate-2-sulfatase (IDS) cDNA from fibroblasts of nine patients with Hunter syndrome (mucopolysaccharidosis type II) was screened for mutations using single strand conformation polymorphism analysis. Direct sequencing revealed a number of different mutations including missense or nonsense point mutations, deletions of one, two, or 60 base pairs, and a 22 base pair-insertion. Mutations of these types probably account for most IDS gene defects as only about 20% of Hunter patients have a complete deletion or gross structural alteration of their IDS gene. Thus the broad clinical variability amongst the Hunter patients may be due to the extensive genetic heterogeneity seen. The relationship between genotype and clinical phenotype is analysed in 12 Hunter patients.
Hum Mol Genet 1992 Aug
PMID:Mutation analysis of the iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II (Hunter syndrome). 130 11

Hunter disease, Mucopolysaccharidosis type II, is an X-linked recessive lysosomal storage disorder caused by a deficiency in iduronate sulfatase activity. We studied at molecular level a Neapolitan family with the disease. We report, in patient, the delta 139 mutation on the third exon of the gene, on female family members, the DNA analysis that allowed to assess or exclude their carrier status and on fetal DNA from a pregnancy of patient's mother, a prenatal diagnosis that resulted negative.
Biochem Mol Biol Int 1995 May
PMID:Molecular genetic characterization and prenatal diagnosis in a family with Hunter disease. 749 64

Hunter syndrome is characterized by a deficiency of iduronate 2-sulfatase. A large number of mutations in the gene have been reported. We describe here the development of a limited primer method for the identification of mutations. In the reaction mixture designed for the limited primer extension, one or two deoxynucleotides from the four necessary deoxynucleotides are added as "selected nucleotides" and another deoxynucleotide which is radiolabeled is added as the "limited nucleotide". The absence of one or two of the deoxynucleotides limits the length of primer elongation, and the low concentration of the "limited nucleotide" causes an "extension-delay" effect and results in a banding pattern upon electrophoresis of the products thus making it possible to distinguish mutant and normal alleles. We have studied three novel mutations in exon IX, 407delTT (TTT to T), 423insCC (CCC to CCCCC), and W502X (TGG to TAG) of the iduronate 2-sulfatase gene by the limited primer extension method.
Biochem Mol Biol Int 1995 May
PMID:Novel use of limited primer extension in detecting mutations in human iduronate 2-sulfatase gene. 749 67

We have recently described the identification of a second IDS locus (IDS-2) located within 90 kb telomeric of the IDS gene (Bondeson et al. submitted). Here, we show that this region is involved in a recombination event with the IDS gene in about 13% of patients with the Hunter syndrome. Analysis of the resulting rearrangement at the molecular level showed that these patients have suffered a recombination event that results in a disruption of the IDS gene in intron 7 with an inversion of the intervening DNA. Interestingly, all of the six cases with a similar type of rearrangement showed recombination between intron 7 of the IDS gene and sequences close to exon 3 at the IDS-2 locus implying that these regions are hot spots for recombination. Analysis by nucleotide sequencing showed that the inversion is caused by recombination between homologous sequences present in the IDS gene and the IDS-2 locus. No detectable deletions or insertions were observed as a result of the recombination event. The results in this study have practical implications for diagnosis of the Hunter syndrome.
Hum Mol Genet 1995 Apr
PMID:Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome. 763 10

The contents of total dolichol were measured in the cerebral cortex of various patients with lysosomal storage disorders, including mucopolysaccharidosis. Strikingly high levels of dolichol were demonstrated in GM1-gangliosides, Sanfilippo B syndrome, and a severe type of Hunter syndrome as well as neuronal ceroid-lipofuscinosis. An increased level of dolichol in cerebral cortex in neuronal ceroid-lipofuscinosis (NCL) was once regarded as pathognomonic for NCL. Our data, however, suggest that an increased level of dolichol in cerebral cortex is a nonspecific phenomenon related to some lysosomal dysfunction secondary to various neurodegenerative disorders.
Mol Chem Neuropathol 1994 Jun
PMID:Elevated levels of dolichol in the brains of mucopolysaccharidosis and related disorders. 791 72

Mutations of the iduronate-2-sulfatase gene were identified in 16 patients with mucopolysaccharidosis type II (Hunter syndrome). Together with another 10 cases reported by us earlier it emerges that about 20% of the patients have deletions of the whole gene or other major structural alterations. One, two or three base pair deletions are found in about 23% of the cases while the remaining about 57% carry point mutations predicting amino acid replacement, premature termination of translation, or aberrant splicing. Molecular analysis of mRNA in splice site mutants showed that these latter defects frequently resulted in use of cryptic splice sites in exons or introns. 62% of the small deletions and point mutations have occurred in 3 of the 9 iduronate-2-sulfatase gene exons. Knowledge of the primary genetic defect allows fast and reliable carrier detection and prenatal diagnosis as well as insight into the relationship between genotype and phenotype.
Hum Mol Genet 1993 Nov
PMID:Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome). 828 Nov 49

The structure of the gene coding for iduronate sulphate sulphatase (IDS) has been determined. We have used exon to exon and vectorette PCR to identify 9 exons within the IDS gene and to characterise the surrounding intron sequences. The results of this study will be useful for the complete analysis of many mutations giving rise to Hunter syndrome. IDS is the first member of the group of lysosomal nonarylsulphatase genes for which the gene structure has been determined. It bears no relationship to the exon organisation of steroid sulphatase, despite the homology between these two proteins. This suggests that the division of the sulphatases into the two subgroups on the basis of substrate specificity is also reflected at the level of gene structure.
Hum Mol Genet 1993 Jan
PMID:Determination of the organisation of coding sequences within the iduronate sulphate sulphatase (IDS) gene. 849 Jun 23

We have previously shown that patients with the Hunter syndrome frequently have suffered from a recombination event between the IDS gene and its putative pseudogene, IDS-2, resulting in an inversion of the intervening DNA. The inversion, which might be the consequence of an intrachromosomal mispairing, is caused by homologous recombination between sequences located in intron 7 of the IDS gene and sequences located distal of exon 3 in IDS-2. In order to gain insight into the mechanisms causing the inversion, we have isolated both inversion junctions in six unrelated patients. DNA sequence analysis of the junctions showed that all recombinations have taken place within a 1 kb region where the sequence identity is >98%. An interesting finding was the identification of regions with alternating IDS gene and IDS-2 sequences present at one inversion junction, suggesting that the recombination event has been initiated by a double-strand break in intron 7 of the IDS gene. The results from this study suggest that homologous recombination in man could be explained by mechanisms similar to those described for Saccharomyces cerevisiae. The results also have practical implications for diagnosis of patients with the Hunter syndrome.
Hum Mol Genet 1997 Apr
PMID:Double-strand breaks may initiate the inversion mutation causing the Hunter syndrome. 909 69

Severe Hunter syndrome is a fatal X-linked lysosomal storage disorder caused by iduronate-2-sulphatase (IDS) deficiency. Patients with complete deletion of the IDS locus often have atypical phenotypes including ptosis, obstructive sleep apnoea, and the occurrence of seizures. We have used genomic DNA sequencing to identify several new genes in the IDS region. DNA deletion patients with atypical symptoms have been analysed to determine whether these atypical symptoms could be due to involvement of these other loci. The occurrence of seizures in two individuals correlated with a deletion extending proximal of IDS, up to and including part of the FMR2 locus. Other (non-seizure) symptoms were associated with distal deletions. In addition, a group of patients with no variant symptoms, and a characteristic rearrangement involving a recombination between the IDS gene and an adjacent IDS pseudogene (IDS psi), showed normal expression of loci distal to IDS. Together, these results identify FMR2 as a candidate gene for seizures, when mutated along with IDS.
Hum Mol Genet 1997 Mar
PMID:Molecular and phenotypic variation in patients with severe Hunter syndrome. 914 53


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