Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human alpha-L-iduronidase (IDUA) gene

Genet Med. 2002 Nov-Dec;4(6):420-6. doi: 10.1097/00125817-200211000-00004.

Abstract

Purpose: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder resulting from a deficiency of the lysosomal glycosidase, alpha-L-iduronidase (IDUA). Patients with MPS I present with variable clinical manifestations ranging from severe to mild. To facilitate studies of phenotype-genotype correlation, the authors performed molecular studies to detect mutations in MPS I patients and characterize single nucleotide polymorphism (SNP) in the gene.

Methods: Twenty-two unrelated MPS I patients were subjects for mutation detection using reverse transcriptional polymerase chain reaction (RT-PCR) and genomic PCR sequencing. Polymorphism analyses were performed on controls by restriction enzyme assays of PCR amplicons flanking nine intragenic single nucleotide polymorphic alleles.

Results: Eleven different mutations including two common mutations (Q70X, W402X), five recurrent mutations (D315Y, P533R, R621X, R628X, S633L), and four novel mutations (R162I, G208D, 1352delG, 1952del25bp) were identified from MPS I patients. Multiple SNP alleles coexisting with the disease-causing mutations were detected. Allelic frequencies for nine SNP alleles including A8, A20, Q33H, L118, N181, A314, A361T, T388, and T410 were determined.

Conclusions: The results provide further evidence for the mutational heterogeneity among MPS I patients and point out possible common haplotype structures in the gene.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Black People
  • Female
  • Gene Frequency
  • Genetic Heterogeneity
  • Genetic Variation
  • Haplotypes
  • Humans
  • Iduronidase / genetics*
  • Male
  • Mucopolysaccharidosis I / enzymology
  • Mucopolysaccharidosis I / genetics*
  • Mutation*
  • Polymorphism, Single Nucleotide*
  • White People

Substances

  • Iduronidase