Mutation {open_quotes}hot spots{close_quotes} in the iduronate-sulfatase gene, and evidence for a pseudogene
- Med. Univ., Luebeck (Germany); and others
Mucopolysaccharidosis type II (Hunter syndrome), iduronate-sulfatase (IDS) deficiency, is an X-linked disorder. Analysis of genomic DNA and cDNA from a total of 60 patients was performed in our laboratory during the last two years. In each case the gene defect was identified, resulting in 41 different mutations, including nonsense, missense, and splice site-point mutations, deletions of various sizes, and a 14 bp duplication. While in only 20% of the patients the whole IDS gene is deleted or largely altered, in about 80% of the cases small deletions (up to 17 bp) and point mutations were found. Of the 9 IDS gene exons, exons III, VIII, and IX harbor 78% of all point mutations, whereas 35% of these latter were found in exon III. Obviously, codon 374 in exon VIII is another mutation {open_quotes}hot spot{close_quotes} as the same point mutation has been found in 7 unrelated patients. Two further {open_quotes}hot spots{close_quotes} are at codons 443 and 468 in exon IX with five different mutations each. Remarkably, all mutations in exon III were found to be heterozygous in the genomic DNA but not in the IDS cDNA of the patients. Of the more than 200 unaffected male controls studied by us, two are heterozygotes for two different point mutations in exon III. Contamination of the samples can be excluded and we hypothesize the existence of a pseudogene that consists of at least exon III. As three patients with submicroscopic deletion and Hunter syndrome show no IDS hybridization signal in Southern analysis, we speculate that the putative pseudogene is in the neighborhood of the functional gene.
- OSTI ID:
- 134300
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1033
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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