A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype

Hamish S. Scott, Tom Litjens, John J. Hopwood, C. Phillip Morris

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63 Citations (Scopus)

Abstract

Mucopolysaccharidosis type I (MPS‐I) is an autosomal recessive genetic disease caused by a deficiency of the glycosidase α‐L‐iduronidase which is required for the lysosomal degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. Patients with MPS‐I store these partially degraded glycosaminoglycans in their lysosomes. MPS‐I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counselling and also impedes the selection and evaluation of patients undergoing therapy such as bone marrow transplantation. We report the presence of a common mutation accounting for 31% of MPS‐I alleles in a study of 64 MPS‐I patients. The mutation was originally detected by chemical cleavage and then direct PCR sequencing. The mutation is a single base substitution that introduces a stop codon at position 402 (W402X) of the α‐L‐iduronidase protein and is associated with an extremely severe clinical phenotype in homozygotes. Patients who are compound heterozygotes having one allele carrying the W402X mutation have a wide range of clinical phenotypes. Based on polymorphisms within the α‐L‐iduronidase gene, W402X is associated with three different haplotypes, implying that there is more than one origin for the mutation or that intragenic recombination has occurred. W402X introduces a MaeI restriction endonuclease site into MPS‐I alleles enabling its simple detection, which should make possible the assessment of the efficacy of bone marrow transplantation in MPS‐I patients homozygous for W402X. © 1992 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalHuman Mutation
Volume1
Issue number2
DOIs
Publication statusPublished or Issued - 1 Jan 1992

Keywords

  • Lysosomal glycosidase
  • Lysosomal storage disorder
  • Scheie syndrome
  • α‐L‐Iduronidase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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