Mutation analysis of phenylketonuria in South Brazil

Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria

“…This mutation is frequently observed in Mediterranean populations [Dworniczak et al, 1991c;Guldberg et al, 1993a;Dianzani et al, 1995;Özgüç et al, 1993;Rivera et al, 1998], strongly indicating these populations as the origin of the IVS10nt-11G→A mutation in our population. Pérez et al [1996] obtained a relative frequency of 16% for the IVS10nt-11G→A mutation, which is similar to that observed in the present study.…”

“…The wide genetic heterogeneity observed in the present study and the analysis of the association between mutations and haplotype indicate a predominantly European origin of these mutations as a consequence of historical migrations, a fact that has also been described for other Latin-American populations [Desviat et al, 1993;Pérez et al, 1996;De Lucca et al, 1998;Pérez et al, 1999]. The Brazilian population originates from a complex racial mixture predominantly of western and southern Europeans, African blacks, and Amerindians.…”

“…To evaluate the genetic heterogeneity of the disease, we analyzed mutations in the PAH gene and the associated haplotypes, and correlated the genotype with the phenotype based on pretreatment phenylalanine levels. Pérez et al [1996] conducted a study on 79 patients with PKU from São Paulo, but their approach to the detection of mutations was very limited since the study was directed only to the search of some mutations (IVS10nt-11G→a, I65T, V388M, R408W, and IVS12nt1G→A) with a high incidence in Europe. In the present study, we used a methodology for efficient mutational screening, i.e., DGGE and broad-range DGGE, which are widely employed for the study of mutations in various populations [Guldberg et al, 1993a;Guldberg et al, 1993b;Hennermann et al, 2000], as well as SSCP for the analysis of some exons of the PAH gene [Labrune et al, 1991;Zschocke et al, 1995;Van der SijsBos et al, 1996].…”

“…The present study shows that the R261Q mutation is mainly associated with haplotype 1.8. Until now, the second most frequent mutation observed in São Paulo was R261Q and not V388M, as reported by Pérez et al [1996].…”

Molecular basis of phenylketonuria in Venezuela: Presence of two novel null mutations

“…Latin America is ethnically very heterogeneous, with each country arising from a particular mixture of Caucasians, Amerindians derived from Mongolian populations, and Negroids from Africa. The analysis of the molecular basis of PKU in Latin American populations has revealed the presence of a mutational spectrum based on the specific demographic profile of each country (Pérez et al, , 1995a(Pérez et al, , 1996Desviat et al, 1995).…”