title: Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.
abstract: Hunter syndrome or mucopolysaccharidoses type II (MPS-II), is a lysosomal storage disorder caused by a deficiency in the activity of the enzyme iduronate-2-sulphatase (IDS). We have investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS-II patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations of the IDS gene were found in DNA from 9 patients two of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoint of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constitute major rearrangements of the gene. Interestingly, six of these rearrangements showed similar or identical patterns by Southern analysis suggestive for a region prone to structural alterations within the IDS gene. We also demonstrate the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. A contiguous gene deletion syndrome characterized by Hunter syndrome and epilepsy is also discussed.
authors.affiliation: Department of Medical Genetics, Uppsala University, Sweden.
authors.forename: M L
authors.initials: ML
authors.lastname: Steén-Bondeson
authors.forename: N
authors.initials: N
authors.lastname: Dahl
authors.forename: T
authors.initials: T
authors.lastname: Tönnesen
authors.forename: W J
authors.initials: WJ
authors.lastname: Kleijer
authors.forename: G
authors.initials: G
authors.lastname: Seidlitz
authors.forename: K H
authors.initials: KH
authors.lastname: Gustavson
authors.forename: P J
authors.initials: PJ
authors.lastname: Wilson
authors.forename: C P
authors.initials: CP
authors.lastname: Morris
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: U
authors.initials: U
authors.lastname: Pettersson
mesh_terms: D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D015342:DNA Probes; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D008297:Male; D016532:Mucopolysaccharidosis II / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D014960:X Chromosome
chemical_list: D015342:DNA Probes; D007066:Iduronate Sulfatase