title: Extension of the molecular analysis to the promoter region of the iduronate 2-sulfatase gene reveals genomic alterations in mucopolysaccharidosis type II patients with normal coding sequence.
abstract: Hunter disease or mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disorder caused by the deficit of the enzyme iduronate-2-sulfatase (IDS), involved in the catabolism of the glycosaminoglycans heparan and dermatan sulfate. Our aim was to search for molecular defects in the promoter region of the IDS gene in patients with previous biochemical diagnosis of MPS II and after we sequenced the whole IDS coding region and the exon/intron boundaries without detecting any pathogenic mutations. Screening of the promoter region of four patients detected in two of them a 178 bp deletion and in the other two a single nucleotide substitution 818 bp upstream of the coding region. The latter had never been described before in MPS II patients and it turned out to be a polymorphism. Our experience suggests that MPS II patients with no mutations detected in the IDS coding region should be screened in the promoter region of the gene. Findings will hopefully help to clarify the relationship between genotype and phenotype and will be useful for the correct molecular diagnosis of Hunter patients and the identification of female carriers, the latter particularly important for genetic counseling.
authors.affiliation: Medical Genetics Service, Hospital de Clinicas, Porto Alegre, RS, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Brusius-Facchin
authors.forename: Luiza
authors.initials: L
authors.lastname: Abrahão
authors.forename: Ida Vanessa Doederlein
authors.initials: IV
authors.lastname: Schwartz
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.forename: Emerson Santana
authors.initials: ES
authors.lastname: Santos
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zanetti
authors.forename: Rosella
authors.initials: R
authors.lastname: Tomanin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Sandra
authors.initials: S
authors.lastname: Leistner-Segal
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D007066:Iduronate Sulfatase / Q000097:blood / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016532:Mucopolysaccharidosis II / Q000175:diagnosis / Q000235:genetics*; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic
chemical_list: D020121:5' Untranslated Regions; D007066:Iduronate Sulfatase
keywords: DMEM; DNA complementary to RNA; Dulbecco's modified Eagle medium; GAGs; Hunter syndrome; IDS; MPS; MPS II; Min; Mutation analysis; PCR; Promoter region; Prot; RPM; Single Nucleotide Polymorphism Database; U/ml; UTR; base pairs; bp; cDNA; centimeters; cm; dbSNPs; del; deletion; glycosaminoglycans; h; hours; iduronate-2-sulfatase; kb; kilobase(s) or 1000 bp; mRNA; messenger ribonucleic acid; mg; micrograms per milliliters; microliters; milligrams; milliliters; minutes; ml; mucopolysaccharidosis; mucopolysaccharidosis type II; nanomoles; nmol; nt; nucleotides; picomoles; pmol; polymerase chain reaction; protein; rotation per minute; units per milliliters; untranslated region; μg/ml; μl