Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

Ursula Matte, Gouri Yogalingam, Doug Brooks, Sandra Leistner, Ida Schwartz, Luciane Lima, Denise Y. Norato, Jaime M. Brum, Clare Beesley, Bryan Winchester, Roberto Giugliani, John J. Hopwood

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, α-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for α-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant α-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalMolecular Genetics and Metabolism
Volume78
Issue number1
DOIs
Publication statusPublished or Issued - 1 Jan 2003

Keywords

  • Expression studies
  • Hurler syndrome
  • Lysosomal storage disorders
  • Mucopolysaccharidosis type I
  • Scheie syndrome
  • α-L-Iduronidase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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