title: Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.
abstract: Hunter syndrome is a human X-linked disorder caused by deficiency of the lysosomal exohydrolase iduronate-2-sulphatase (IDS). The consequent accumulation of the mucopolysaccharides dermatan sulphate and heparan sulphate, in the brain and other tissues, often results in death before adulthood. There is, however, a broad spectrum of severity that has been attributed to different mutations of the Hunter syndrome gene. We have used an IDS cDNA clone to localise the IDS gene to Xq28, distal to the fragile X mutation (FRAXA). One-third of Hunter syndrome patients had various deletions or rearrangements of their IDS gene, proving that different mutations are common in this condition. Deletions of the IDS gene can include a conserved locus that is tightly linked to FRAXA, suggesting that deletion of nearby genes may contribute to the variable clinical severity noted in Hunter syndrome. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation.
authors.affiliation: Department of Chemical Pathology, Adelaide Children's Hospital, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wilson
authors.forename: G K
authors.initials: GK
authors.lastname: Suthers
authors.forename: D F
authors.initials: DF
authors.lastname: Callen
authors.forename: E
authors.initials: E
authors.lastname: Baker
authors.forename: P V
authors.initials: PV
authors.lastname: Nelson
authors.forename: A
authors.initials: A
authors.lastname: Cooper
authors.forename: J E
authors.initials: JE
authors.lastname: Wraith
authors.forename: G R
authors.initials: GR
authors.lastname: Sutherland
authors.forename: C P
authors.initials: CP
authors.lastname: Morris
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D015139:Blotting, Southern; D002478:Cells, Cultured; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D005260:Female; D015321:Gene Rearrangement; D008040:Genetic Linkage; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D008297:Male; D016532:Mucopolysaccharidosis II / Q000201:enzymology / Q000235:genetics*; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D007066:Iduronate Sulfatase