title: DNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.
abstract: Deficiency of the enzyme iduronate-2-sulfatase (IDS) results in Hunter syndrome, an X-linked recessive lysosomal storage disorder. In this study, analysis of a patient with features of moderate to severe Hunter syndrome identified a 178-bp deletion upstream of IDS exon 1 spanning a predicted promoter element. Sequencing of all nine IDS exons from this patient failed to identify any additional mutations within the coding regions or in intron-exon boundaries. The 178-bp deletion is flanked by two 13-bp direct repeats and potential DNA topoisomerase II recognition sites. These findings point toward nonhomologous recombination as a possible mechanism for this mutation. Expression studies on this patient do not detect any IDS transcripts, indicating that the deletion spans sequences essential for IDS expression. Complete lack of expression of IDS is consistent with the moderate to severe phenotype observed in this patient.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Timms
authors.forename: L E
authors.initials: LE
authors.lastname: Huckett
authors.forename: J W
authors.initials: JW
authors.lastname: Belmont
authors.forename: S K
authors.initials: SK
authors.lastname: Shapira
authors.forename: R A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016532:Mucopolysaccharidosis II / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D007066:Iduronate Sulfatase