An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity

Stefano Regis, Mirella Filocamo, Fabio Corsolini, Francesco Caroli, Joke L M Keulemans, Otto P. Van Diggelen, Rosanna Gatti

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Sphingolipid activator proteins are small glycoproteins required for the degradation of sphingolipids by specific lysosomal hydrolases. Four of them, called saposins, are encoded by the prosaposin gene, the product of which is proteolytically cleaved into the four mature saposin proteins (saposins A, B, C, D). One of these, saposin B, is necessary in the hydrolysis of sulphatide by arylsulphatase A where it presents the solubilised substrate to the enzyme. As an alternative to arylsulphatase A deficiency, deficiency of saposin B causes metachromatic leukodystrophy. We identified a previously undescribed mutation (N215K) in the prosaposin gene of a patient with metachromatic leukodystrophy but with normal arylsulphatase A activity and elevated sulphatide in urine. The mutation involves a highly conserved amino acidic residue and abolishes the only N-glycosylation site of saposin B.

Original languageEnglish
Pages (from-to)125-130
Number of pages6
JournalEuropean Journal of Human Genetics
Volume7
Issue number2
Publication statusPublished - Feb 1999

Fingerprint

Saposins
Cerebroside-Sulfatase
Metachromatic Leukodystrophy
Glycosylation
Sulfoglycosphingolipids
Sphingolipid Activator Proteins
Mutation
Sphingolipids
Hydrolases
Genes
Glycoproteins
Hydrolysis
Urine
Enzymes

Keywords

  • Cerebroside sulphate activator
  • Metachromatic leukodystrophy
  • Sphingolipid activator proteins

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

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title = "An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity",
abstract = "Sphingolipid activator proteins are small glycoproteins required for the degradation of sphingolipids by specific lysosomal hydrolases. Four of them, called saposins, are encoded by the prosaposin gene, the product of which is proteolytically cleaved into the four mature saposin proteins (saposins A, B, C, D). One of these, saposin B, is necessary in the hydrolysis of sulphatide by arylsulphatase A where it presents the solubilised substrate to the enzyme. As an alternative to arylsulphatase A deficiency, deficiency of saposin B causes metachromatic leukodystrophy. We identified a previously undescribed mutation (N215K) in the prosaposin gene of a patient with metachromatic leukodystrophy but with normal arylsulphatase A activity and elevated sulphatide in urine. The mutation involves a highly conserved amino acidic residue and abolishes the only N-glycosylation site of saposin B.",
keywords = "Cerebroside sulphate activator, Metachromatic leukodystrophy, Sphingolipid activator proteins",
author = "Stefano Regis and Mirella Filocamo and Fabio Corsolini and Francesco Caroli and Keulemans, {Joke L M} and {Van Diggelen}, {Otto P.} and Rosanna Gatti",
year = "1999",
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language = "English",
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T1 - An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity

AU - Regis, Stefano

AU - Filocamo, Mirella

AU - Corsolini, Fabio

AU - Caroli, Francesco

AU - Keulemans, Joke L M

AU - Van Diggelen, Otto P.

AU - Gatti, Rosanna

PY - 1999/2

Y1 - 1999/2

N2 - Sphingolipid activator proteins are small glycoproteins required for the degradation of sphingolipids by specific lysosomal hydrolases. Four of them, called saposins, are encoded by the prosaposin gene, the product of which is proteolytically cleaved into the four mature saposin proteins (saposins A, B, C, D). One of these, saposin B, is necessary in the hydrolysis of sulphatide by arylsulphatase A where it presents the solubilised substrate to the enzyme. As an alternative to arylsulphatase A deficiency, deficiency of saposin B causes metachromatic leukodystrophy. We identified a previously undescribed mutation (N215K) in the prosaposin gene of a patient with metachromatic leukodystrophy but with normal arylsulphatase A activity and elevated sulphatide in urine. The mutation involves a highly conserved amino acidic residue and abolishes the only N-glycosylation site of saposin B.

AB - Sphingolipid activator proteins are small glycoproteins required for the degradation of sphingolipids by specific lysosomal hydrolases. Four of them, called saposins, are encoded by the prosaposin gene, the product of which is proteolytically cleaved into the four mature saposin proteins (saposins A, B, C, D). One of these, saposin B, is necessary in the hydrolysis of sulphatide by arylsulphatase A where it presents the solubilised substrate to the enzyme. As an alternative to arylsulphatase A deficiency, deficiency of saposin B causes metachromatic leukodystrophy. We identified a previously undescribed mutation (N215K) in the prosaposin gene of a patient with metachromatic leukodystrophy but with normal arylsulphatase A activity and elevated sulphatide in urine. The mutation involves a highly conserved amino acidic residue and abolishes the only N-glycosylation site of saposin B.

KW - Cerebroside sulphate activator

KW - Metachromatic leukodystrophy

KW - Sphingolipid activator proteins

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