Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Pará

Abstract Background Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Pará in the North Region of Brazil. Methods All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non‐PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records. Results Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10‐11G>A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype. Conclusion In PKU patients from state of Pará, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula

Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para

Laboratory of Inborn Errors of Metabolism of the Federal University of Pará in the performance of laboratory testsFederal University of Pará. Institute of Biological Sciences. Laboratory of Inborn Errors of Metabolism. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará.Institute of Health Sciences. Faculty of Nutrition. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Human and Medical Genetics. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Inborn Errors of Metabolism. Belém, PA, Brazil.Background: Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Pará in the North Region of Brazil. Methods: All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non-PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records. Results: Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10-11G>A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype. Conclusion: In PKU patients from state of Pará, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula