title: Molecular characterization of phenylketonuria in South Brazil.
abstract: Phenylketonuria (PKU) is an autosomal recessive disorder due to phenylalanine hydroxylase (PAH) deficiency. The PAH gene, located at 12q22-q24.1, includes about 90kb and contains 13 exons. To date, more than 420 different alterations have been identified in the PAH gene. To determine the nature and frequency of PAH mutations in PKU patients from South Brazil, mutation analysis was performed on genomic DNA from 23 unrelated PKU patients. The 13 exons and flanking regions of the PAH gene were amplified by PCR and the amplicons were analyzed by single strand conformation polymorphism (SSCP). Amplicons that showed abnormal migration patterns were analyzed by restriction endonuclease digestion and/or sequencing. Twenty-two previously reported mutations were identified including R261X, R408W, IVS2nt5g-->c, R261Q, and V388M. Polymorphisms were observed in 48.8% of the PKU patients, the most frequent being IVS2nt19t-->c, V245V, and IVS12nt-35c-->t. In addition, two novel sequence variants were identified: 1378g-->t in the 3(')-untranslated region in exon 13 which may be disease-causing and an intron 12 polymorphism, IVS12nt-15t-->c. The mutation spectrum in the patients from Southern Brazil differed from that observed in patients from other Latin American countries and further defined the molecular heterogeneity of this disease.
authors.affiliation: Department of Biochemistry, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Santana da Silva
authors.forename: Tiago Santos
authors.initials: TS
authors.lastname: Carvalho
authors.forename: Fernanda Britto
authors.initials: FB
authors.lastname: da Silva
authors.forename: Liana
authors.initials: L
authors.lastname: Morari
authors.forename: Angela Aguirres
authors.initials: AA
authors.lastname: Fachel
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pires
authors.forename: Lília Farret
authors.initials: LF
authors.lastname: Refosco
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva Pereira
mesh_terms: D001938:Brazil / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000172:deficiency; D010661:Phenylketonurias / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D015183:Restriction Mapping
chemical_list: D010651:Phenylalanine Hydroxylase