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| Author(s): |
Angelina Xavier Acosta
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2001-01-23 |
| Examining board members: |
Marco Antonio Zago;
Roberto Giugliani;
João Monteiro de Pina Neto;
Wilson Araújo da Silva Junior;
Marilia de Arruda Cardoso Smith
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| Advisor: | Marco Antonio Zago |
| Abstract | |
ln the present study, 115 Brazilian families with phenylketonuria (PKU), mainly from the Southeast, were studied using three laboratory methods (DGGE, SSCP and sequencing). AII 13 exons of the PAH gene were analyzed, including the splicing sites and the prometer region. We identified 50 distinct mutations and characterized 91% of the mutant alleles. The 5 most prevalent mutations of the 50 mutations identified (50% of the PKU alleles) were IVS10nt-11g→a (17.4%), followed by R261Q (12.2%), V388M (9.1%), R252W (6.5%) and R270K (4.8%). The other mutations were rare. The mutation spectrum included 10 new mutations (IVS5nt-54a→g, IVS6nt17g→t, E205A, F240S, K274E, I318T, L321L, C357G, IVS11nt17g→a and S411X). To characterize the origin and distribution of the PAH alleles we determined the association between the detected mutations and the PCR/RFLP haplotypes and VNTR alleles located on the PAH gene. For those patients whose mutant alleles were detected we calculated the correlation with pretreatment phenylalanine levels, thus establishing a genotype/phenotype correlation. The present results confirm the marked heterogeneity observed at the PAH locus and contribute to the understanding of the distribution and frequency of PKU mutations in the Brazilian population. (AU) | |