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An N‐acetylgalactosamine‐4‐sulfatase mutation (ΔG238) results in a severe Maroteaux‐Lamy phenotype

An N‐acetylgalactosamine‐4‐sulfatase mutation (ΔG238) results in a severe Maroteaux‐Lamy phenotype Maroteaux‐Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomally inherited lysosomal storage disorder caused by a deficiency of N‐acetylgalactosamine‐4‐sulfatase (EC 3.1.6.1; 4‐sulfatase). In order to determine the gene defect in a clinically severe MPS VI patient, polymerase chain reaction (PCR) products were generated from the patient's fibroblast mRNA and also from a 4‐sulfatase cDNA clone and subjected to the chemical cleavage technique to detect mismatched bases, which were then identified by direct DNA sequencing of the PCR products. The patient was homozygous for an early frameshift mutation caused by the deletion of a G at position 238 (ΔG238), which produces a truncated 4‐sulfatase with an altered amino acid sequence from amino acid 80 to a premature stop codon at codon 113 relative to the normal 4‐sulfatase reading frame of 533 amino acids. Since the mutation occurs only 40 amino acids past the signal peptidase cleavage site, it is most likely that this will result in a protein with no 4‐sulfatase activity. This is consistent with the severe clinical presentation and the absence of 4‐sulfatase enzyme activity or mutant 4‐sulfatase protein in the patient. The patient was also found to be homozygous for two polymorphisms, i.e., a G to A transition at nucleotide 1072 resulting in a valine358 to methionine substitution (V358M) and a silent A to G transition in the third base of the proline397 codon at nucleotide 1191. © 1992 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Mutation Wiley

An N‐acetylgalactosamine‐4‐sulfatase mutation (ΔG238) results in a severe Maroteaux‐Lamy phenotype

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References (25)

Publisher
Wiley
Copyright
Copyright © 1992 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1059-7794
eISSN
1098-1004
DOI
10.1002/humu.1380010509
pmid
1301949
Publisher site
See Article on Publisher Site

Abstract

Maroteaux‐Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomally inherited lysosomal storage disorder caused by a deficiency of N‐acetylgalactosamine‐4‐sulfatase (EC 3.1.6.1; 4‐sulfatase). In order to determine the gene defect in a clinically severe MPS VI patient, polymerase chain reaction (PCR) products were generated from the patient's fibroblast mRNA and also from a 4‐sulfatase cDNA clone and subjected to the chemical cleavage technique to detect mismatched bases, which were then identified by direct DNA sequencing of the PCR products. The patient was homozygous for an early frameshift mutation caused by the deletion of a G at position 238 (ΔG238), which produces a truncated 4‐sulfatase with an altered amino acid sequence from amino acid 80 to a premature stop codon at codon 113 relative to the normal 4‐sulfatase reading frame of 533 amino acids. Since the mutation occurs only 40 amino acids past the signal peptidase cleavage site, it is most likely that this will result in a protein with no 4‐sulfatase activity. This is consistent with the severe clinical presentation and the absence of 4‐sulfatase enzyme activity or mutant 4‐sulfatase protein in the patient. The patient was also found to be homozygous for two polymorphisms, i.e., a G to A transition at nucleotide 1072 resulting in a valine358 to methionine substitution (V358M) and a silent A to G transition in the third base of the proline397 codon at nucleotide 1191. © 1992 Wiley‐Liss, Inc.

Journal

Human Mutation – Wiley

Published: Jan 1, 1992

Keywords: Maroteaux–Lamy syndrome; Mucopolysaccharidosis type VI; N‐Acetylgalactosamine‐4‐sulfatase; Arylsulfatase B; Gene mutation; Clinical phenotype; Genotype–phenotype correlation

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