title: Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients.
abstract: In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Brusius-Facchin
authors.affiliation: Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil; Department of Genetics, UFRGS, Porto Alegre, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil.
authors.forename: I V D
authors.initials: IV
authors.lastname: Schwartz
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Zimmer
authors.affiliation: Clinical Genetics Service, IPPMG, UFRJ, Rio de Janeiro, Brazil.
authors.forename: M G
authors.initials: MG
authors.lastname: Ribeiro
authors.affiliation: Department of Pediatrics, UFBA, Salvador, Brazil.
authors.forename: A X
authors.initials: AX
authors.lastname: Acosta
authors.affiliation: Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Horovitz
authors.affiliation: Department of Pediatrics, UNCISAL, Maceió, Brazil.
authors.forename: I L
authors.initials: IL
authors.lastname: Monlleó
authors.affiliation: Department of Pediatrics, UNCISAL, Maceió, Brazil.
authors.forename: M I B
authors.initials: MI
authors.lastname: Fontes
authors.affiliation: Department of Molecular Biology, FAMERP, São José do Rio Preto, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Fett-Conte
authors.affiliation: Department of Medical Genetics, UNICAMP, Campinas, Brazil.
authors.forename: R P Oliveira
authors.initials: RP
authors.lastname: Sobrinho
authors.affiliation: Medical Genetics Service, IMIP, Recife, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Duarte
authors.affiliation: Mother and Child Department, UERJ, Rio de Janeiro, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Boy
authors.affiliation: Genetics and Metabolic Diseases Unit, INTA, University of Chile, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Mabe
authors.affiliation: Department of Genetics, ILCS-UNA, Asunción, Paraguay.
authors.forename: M
authors.initials: M
authors.lastname: Ascurra
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: M
authors.initials: M
authors.lastname: de Michelena
authors.affiliation: Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Tylee
authors.affiliation: Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: G T N
authors.initials: GT
authors.lastname: Besley
authors.affiliation: Unidad de Genética Clínica, Hospital Roberto del Río, Santiago, Chile.
authors.forename: M C V
authors.initials: MC
authors.lastname: Garreton
authors.affiliation: Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil; Department of Genetics, UFRGS, Porto Alegre, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil; Department of Genetics, UFRGS, Porto Alegre, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Brazil. Electronic address: ssegal@hcpa.ufrgs.br.
authors.forename: S
authors.initials: S
authors.lastname: Leistner-Segal
mesh_terms: D000328:Adult; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D016532:Mucopolysaccharidosis II / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D013020:South America
chemical_list: D007066:Iduronate Sulfatase
keywords: Genotype–phenotype correlation; Glycosaminoglycans; Hunter syndrome; Iduronate-2-sulfatase; Mucopolysaccharidosis type II