2000
DOI: 10.1023/a:1005603014401
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A non‐glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP‐B) in a novel case of metachromatic leukodystrophy (MLD)

Abstract: The lysosomal degradation of sphingolipids with short oligosaccharide chains depends on small glycosylated non-enzymatic sphingolipid activator proteins (SAPs, saposins). Four of the five known SAPs, SAP-A, -B, -C and -D, are derived by proteolytic processing from a common precursor protein (SAP-precursor) that is encoded by a gene on chromosome 10 consisting of 15 exons and 14 introns. SAP-B is a non-specific glycolipid binding protein that stimulates in vitro the hydrolysis of about 20 glycolipids by differe… Show more

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Cited by 35 publications
(9 citation statements)
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“…These cross linkages might account for the unusual stability against pH (1.5-12), heat (up to 95°C) and proteases (Gärtner et al 1983). Until now, five point mutations on the SAP-B domain of the SAP-precursor gene have been identified (Wrobe et al 2000).…”
Section: (C) Enzymologymentioning
confidence: 99%
“…These cross linkages might account for the unusual stability against pH (1.5-12), heat (up to 95°C) and proteases (Gärtner et al 1983). Until now, five point mutations on the SAP-B domain of the SAP-precursor gene have been identified (Wrobe et al 2000).…”
Section: (C) Enzymologymentioning
confidence: 99%
“…To date, 7 mutations have been reported to cause sphingolipid activator protein B deficiency. [10][11][12][13][14][15][16][17][18]20 Of note, with the exception of 1 Italian case (patient 11), all these mutations were in the homozygous state 6 even in the families where consanguinity was not reported. The mutations were single-nucleotide substitutions in all patients except a French Canadian woman who had a 33-base insertion at the location of the normal 9-base exon site, and she was the only reported case with the adult-onset variant.…”
Section: Discussionmentioning
confidence: 99%
“…To the best of our knowledge, to date only 15 cases have been reported in the literature with sphingolipid activator protein B deficiency. 4,[7][8][9][10][11][12][13][14] Here, we present the clinical and molecular findings of 9 children from 4 unrelated Saudi families with sphingolipid activator protein B deficiency. Interestingly, when we reviewed our series of patients with metachromatic leukodystrophy in our tertiary center, we found sphingolipid activator protein B-deficient metachromatic leukodystrophy to be more common than the classic arylsulfatase A-deficient metachromatic leukodystrophy.…”
mentioning
confidence: 99%
“…Two cases of an Asn to Lys substitution (N21K using the CSAct nomenclature, or N215K using the precursor prosaposin nomenclature) at the glycosylation site have been reported. 18,19 This mutation, which results in loss of a highly conserved amino acid residue and abolishes the only N-glycosylation site of the protein, causes severe and progressive neurological deterioration. Another form of activator-deficient metachromatic leukodystrophy is caused by a single point mutation (C-T transition) in the open reading frame resulting in a substitution of isoleucine for threonine (T23I using the CSAct nomenclature, or T217I using the precursor prosaposin nomenclature) and loss of the glycosylation recognition site.…”
Section: Introduction †mentioning
confidence: 99%