Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The terminal part of the short arm of the human X chromosome has been mapped by pulsed-field gel electrophoresis (PFGE). The map, representing the distal two-thirds of Xp22.3 spans a total of 10,000 kilobases (kb) from Xpter to the DXS143 locus. A comparison with linkage data indicates that 1 centimorgan (cM) in this region corresponds to about 600 kb. CpG islands were essentially concentrated in the 1500 kb immediately proximal to the pseudoautosomal boundary. Several loci, including the gene encoding steroid sulfatase (STS) and the loci for the X-linked recessive form of chondrodysplasia punctata (CDPX) and for Kallmann syndrome (KAL) have been placed relative to the Xp telomere. CDPX is located between 2650 and 5550 kb from Xpter, and STS is located between 7250 and 7830 kb from Xpter. KAL maps to an interval of 350 kb between 8600 and 8950 kb from the telomere. The X-chromosomal breakpoints of a high proportion of XX males resulting from X-Y interchange cluster to a 920-kb region proximal and close to the pseudoautosomal boundary.
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PMID:Long-range restriction map of the terminal part of the short arm of the human X chromosome. 233 11

X-linked recessive chondrodysplasia punctata (CDPX) is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. A virtually identical phenotype is observed in the warfarin embryopathy, which is due to the teratogenic effects of coumarin derivatives during pregnancy. We have cloned the genomic region within Xp22.3 where the CDPX gene has been assigned and isolated three adjacent genes showing highly significant homology to the sulfatase gene family. Point mutations in one of these genes were identified in five patients with CDPX. Expression of this gene in COS cells resulted in a heat-labile arylsulfatase activity that is inhibited by warfarin. A deficiency of a heat-labile arylsulfatase activity was demonstrated in patients with deletions spanning the CDPX region. These data indicate that CDPX is caused by an inherited deficiency of a novel sulfatase and suggest that warfarin embryopathy might involve drug-induced inhibition of the same enzyme.
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PMID:A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy. 772 70

X-linked chondrodysplasia punctata (CDPX) is a congenital disorder characterized by abnormalities in cartilage and bone development. Mutations leading to amino acid substitutions were identified recently in CDPX patients, in the coding region of the arylsulfatase E (ARSE) gene, a novel member of the sulfatase gene family. Transfection of the ARSE full-length cDNA, in Cos7 cells, allowed us to establish that its protein product is a 60-kD precursor, which is subject to N-glycosylation, to give a mature 68-kD form that, unique among sulfatases, is localized to the Golgi apparatus. Five missense mutations found in CDPX patients were introduced into wild-type ARSE cDNA by site-directed mutagenesis. These mutants were transfected into Cos7 cells, and the arylsulfatase activity and biochemical properties were determined, to study the effect of these substitutions on the ARSE protein. One of the mutants behaves as the wild-type protein. All four of the other mutations resulted in a complete lack of arylsulfatase activity, although the substitutions do not appear to affect the stability and subcellular localization of the protein. The loss of activity due to these mutations confirms their involvement in the clinical phenotype and points to the importance of these residues in the correct folding of a catalytically active ARSE enzyme.
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PMID:Biochemical characterization of arylsulfatase E and functional analysis of mutations found in patients with X-linked chondrodysplasia punctata. 949 43

Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. Deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either GAGs (glycosaminoglycans) or sulfolipids. The catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. This modification is performed by SUMF1 (sulfatase-modifying factor 1), which is an essential factor for sulfatase activities. Mutations in the SUMF1 gene cause MSD (multiple sulfatase deficiency), an autosomal recessive disease in which the activities of all sulfatases are profoundly reduced. In previous studies, we have shown that SUMF1 has an enhancing effect on sulfatase activity when co-expressed with sulfatase genes in COS-7 cells. In the present study, we demonstrate that SUMF1 displays an enhancing effect on sulfatases activity when co-delivered with a sulfatase cDNA via AAV (adeno-associated virus) and LV (lentivirus) vectors in cells from individuals affected by five different diseases owing to sulfatase deficiencies or from murine models of the same diseases [i.e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]. The SUMF1-enhancing effect on sulfatase activity resulted in an improved clearance of the intracellular GAG or sulfolipid accumulation. Moreover, we demonstrate that the SUMF1-enhancing effect is also present in vivo after AAV-mediated delivery of the sulfamidase gene to the muscle of MPSIIIA mice, resulting in a more efficient rescue of the phenotype. These results indicate that co-delivery of SUMF1 may enhance the efficacy of gene therapy in several sulfatase deficiencies.
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PMID:SUMF1 enhances sulfatase activities in vivo in five sulfatase deficiencies. 1720 39

X-linked Recessive Chondrodysplasia Punctata (CDPX1) is due to a defect in arylsulfatase E (ARSE), located on Xp22.3. Neither the substrate nor function of the encoded warfarin-sensitive arylsulfatase has been identified and molecular analysis remains the only confirmatory diagnostic test. Nevertheless, the majority of patients evaluated have not had identifiable mutations in ARSE, and thus far 23 patients have been reported. The major clinical features in these patients are also present in a group now recognized as phenocopies, due to vitamin K deficiency in early gestation or maternal autoimmune disease. We evaluated the ARSE gene in 11 patients who met clinical criteria for CDPX1. We amplified all exons and intronic flanking sequence from each patient, and investigated suspected deletions or rearrangements by southern analysis. We identified mutations in seven individuals. Of the remainder, three had maternal conditions that further expand the phenocopy group. Thus, this group might represent a proportion of the mutation-negative patients in previous studies. We extracted clinical information from all prior reports over the past decade and show that there are few distinguishing features on examination between these two groups of patients. This study supports heterogeneity for CDPX1-like phenotypes and sorting these out will help to define the biological pathway and genetic contributors.
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PMID:Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata. 1834 68