Mucopolysaccharidosis type II (Hunter syndrome): mutation "hot spots" in the iduronate-2-sulfatase gene

Am J Hum Genet. 1996 Dec;59(6):1202-9.


Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-chromosomal storage disorder due to deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). We have identified IDS mutations in a total of 31 families/patients with MPS II, of which 20 are novel and unique and a further 1 is novel but has been found in 3 unrelated patients. One of the mutations detected is of special interest as an AG-->G substitution in an intron, far apart from the coding region, is deleterious by creating a new 5'-splice-donor site that results in the inclusion of a 78-bp intronic sequence. While the distribution of gene rearrangements (deletions, insertions, and duplications) of <20 bp seems to be random over the IDS gene, the analysis of a total of 101 point mutations lying within the coding region shows that they tend to be more frequent in exons III, VIII, and IX. Forty-seven percent of the point mutations are at CpG dinucleotides, of which G:C-to-A:T transitions constitute nearly 80%. Almost all recurrent point mutations involve CpG sites. Analysis of a collective of 50 families studied in our laboratory, to date, revealed that mutations occur more frequently in male meioses (estimated male-to-female ratio between 3.76 and 6.3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Base Sequence
  • Female
  • Gene Rearrangement*
  • Genetic Linkage
  • Genotype
  • Heterozygote
  • Humans
  • Iduronate Sulfatase / genetics*
  • Male
  • Molecular Sequence Data
  • Mucopolysaccharidosis II / ethnology
  • Mucopolysaccharidosis II / genetics*
  • Phenotype
  • Point Mutation / genetics*
  • RNA, Messenger / genetics
  • X Chromosome / genetics*


  • RNA, Messenger
  • Iduronate Sulfatase