title: Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in brief no. 233. Online.
abstract: Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6 unrelated patients with Hunter syndrome to assess genotype/phenotype relationships and offer carrier testing where required. Six novel mutations were identified: four missense mutations, one four-base pair deletion (596-599delAACA) and a cryptic splice site mutation. Three of the missense mutations were significant amino acid substitutions (S143F, S491F, E341K) of which the latter two involve amino acids conserved amongst sulfatase enzymes. The patients identified with these mutations all had a severe clinical phenotype. One missense mutation with a minimal amino acid substitution (H342Y), in a non-conserved region of the gene, was associated with a mild clinical phenotype. We identified a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA processing. We predict that the normal mRNA product confered some residual functional enzyme, resulting in a mild phenotype associated with the absence of overt central nervous system disease.
authors.affiliation: Department of Pathology, University of British Columbia, Vancouver, Canada. hvallance@wpog.childhosp.bc.ca
authors.forename: H D
authors.initials: HD
authors.lastname: Vallance
authors.forename: L
authors.initials: L
authors.lastname: Bernard
authors.forename: M
authors.initials: M
authors.lastname: Rashed
authors.forename: D
authors.initials: D
authors.lastname: Chiu
authors.forename: G
authors.initials: G
authors.lastname: Le
authors.forename: J
authors.initials: J
authors.lastname: Toone
authors.forename: D A
authors.initials: DA
authors.lastname: Applegarth
authors.forename: M
authors.initials: M
authors.lastname: Coulter-Mackie
mesh_terms: D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D016532:Mucopolysaccharidosis II / Q000235:genetics; D020125:Mutation, Missense; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D012333:RNA, Messenger; D007066:Iduronate Sulfatase