Mutation {open_quotes}hot spots{close_quotes} in the iduronate-sulfatase gene, and evidence for a pseudogene

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134300

Rathmann, M; Bunge, S; Gal, A ^[1]

---

1. 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--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CODONS
DNA HYBRIDIZATION
ESTERASES
EXONS
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN X CHROMOSOME
MALES
METABOLIC DISEASES
SPLICING