Molecular characterization of phenylketonuria in South Brazil

Luiz Carlos Santana Da Silva, Tiago Santos Carvalho, Fernanda Britto Da Silva, Liana Morari, Ângela Aguirres Fachel, Ricardo Pires, Lília Farret Refosco, Robert J. Desnick, Roberto Giugliani, Maria Luiza Saraiva Pereira

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number1
StatePublished - 1 May 2003
Externally publishedYes


Dive into the research topics of 'Molecular characterization of phenylketonuria in South Brazil'. Together they form a unique fingerprint.

Cite this