A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type D (MPS IIID)

Wang, He; Voznyi, Ya. V.; Boer, A. M.; Kleijer, Wim J.; Diggelen, O. P. van

doi:10.1007/bf00711508

Cited by 67 publications

(30 citation statements)

References 19 publications

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“…Precipitation of GAG for two-dimensional electrophoresis was performed according to Whiteman and Henderson (1977) and GAG electrophoresis according to Abeling et al (Abeling et al, 1974). The enzyme activity of α-N-acetylglucosamine-6-sulphatase was determined with the fluorogenic substrate (Moscerdam Substrates) as described (He et al, 1993).…”

Section: Gag Determination and Enzyme Analysismentioning

confidence: 99%

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

et al. 2010

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Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 inframe small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.

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Section: Gag Determination and Enzyme Analysismentioning

confidence: 99%

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

et al. 2010

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“…ARSF activity was tested as described in Puca et al [1997]. Iduronate 2-sulfatase, heparan N-sulfatase, N-acetylglucosamine 6-sulfatase and galactose 6-sulfatase were assayed with fluorogenic substrates as previously described [He et al, 1993;Karpova et al, 1996;van Diggelen et al, 1990;Voznyi et al, 2001].…”

Section: Sulfatase Enzymatic Assaysmentioning

confidence: 99%

Molecular and functional analysis ofSUMF1 mutations in multiple sulfatase deficiency

et al. 2004

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Multiple sulfatase deficiency (MSD) is a rare disorder characterized by impaired activity of all known sulfatases. The gene mutated in this disease is SUMF1, which encodes a protein involved in a post-translational modification at the catalytic site of all sulfatases that is necessary for their function. SUMF1 strongly enhances the activity of sulfatases when coexpressed with sulfatase in Cos-7 cells. We performed a mutational analysis of SUMF1 in 20 MSD patients of different ethnic origin. The clinical presentation of these patients was variable, ranging from severe neonatal forms to mild phenotypes showing mild neurological involvement. A total of 22 SUMF1 mutations were identified, including missense, nonsense, microdeletion, and splicing mutations. We expressed all missense mutations in culture to study their ability to enhance the activity of sulfatases. Of the predicted amino acid changes, 11 (p.R349W, p.R224W, p.L20F, p.A348P, p.S155P, p.C218Y, p.N259I, p.A279V, p.R349Q, p.C336R, p.A177P) resulted in severely impaired sulfatase-enhancing activity. Two (p.R345C and p.P266L) showed a high residual activity on some, but not all, of the nine sulfatases tested, suggesting that some SUMF1 mutations may have variable effects on the activity of each sulfatase. This study compares, for the first time, clinical, biochemical, and molecular data in MSD patients. Our results show lack of a direct correlation between the type of molecular defect and the severity of phenotype.

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“…2-dimensional electrophoresis (2-DE) was performed with standard Alcian blue reagent method [4]. Enzyme assays were performed by using artificial fluorigenic (4-methylumbelliferyl) and chromogenic substrates [5][6][7][8][9][10][11][12][13][14].…”

Section: Methodsmentioning

confidence: 99%