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Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients

Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, fr...

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Autores principales: Tresbach, Rafael Hencke, Sperb-Ludwig, Fernanda, Ligabue-Braun, Rodrigo, Tonon, Tássia, de Oliveira Cardoso, Maria Teresinha, Heredia, Romina Soledad, da Silva Rosa, Maria Teresa Alves, Martins, Bárbara Cátia, Poubel, Monique Oliveira, da Silva, Luiz Carlos Santana, Maillot, François, Schwartz, Ida Vanessa Doederlein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824641/
https://www.ncbi.nlm.nih.gov/pubmed/33375644
http://dx.doi.org/10.3390/genes12010020
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author Tresbach, Rafael Hencke
Sperb-Ludwig, Fernanda
Ligabue-Braun, Rodrigo
Tonon, Tássia
de Oliveira Cardoso, Maria Teresinha
Heredia, Romina Soledad
da Silva Rosa, Maria Teresa Alves
Martins, Bárbara Cátia
Poubel, Monique Oliveira
da Silva, Luiz Carlos Santana
Maillot, François
Schwartz, Ida Vanessa Doederlein
author_facet Tresbach, Rafael Hencke
Sperb-Ludwig, Fernanda
Ligabue-Braun, Rodrigo
Tonon, Tássia
de Oliveira Cardoso, Maria Teresinha
Heredia, Romina Soledad
da Silva Rosa, Maria Teresa Alves
Martins, Bárbara Cátia
Poubel, Monique Oliveira
da Silva, Luiz Carlos Santana
Maillot, François
Schwartz, Ida Vanessa Doederlein
author_sort Tresbach, Rafael Hencke
collection PubMed
description Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, from 33 unrelated families, were analyzed through next-generation sequencing in the Ion Torrent PGM™ platform. Phenotype–genotype correlations were made based on the BioPKU database. Three patients required additional Sanger sequencing analyses. Twenty-six different pathogenic variants were identified. The most frequent variants were c.1315+1G>A (n = 8/66), c.473G>A (n = 6/66), and c.1162G>A (n = 6/66). One novel variant, c.524C>G (p.Pro175Arg), was found in one allele and was predicted as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) criteria. The molecular modeling of p.Pro175Arg indicated that this substitution can affect monomers binding in the PAH tetramer, which could lead to a change in the stability and activity of this enzyme. Next-generation sequencing was a fast and effective method for diagnosing PKU and is useful for patient phenotype prediction and genetic counseling.
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spelling pubmed-78246412021-01-24 Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients Tresbach, Rafael Hencke Sperb-Ludwig, Fernanda Ligabue-Braun, Rodrigo Tonon, Tássia de Oliveira Cardoso, Maria Teresinha Heredia, Romina Soledad da Silva Rosa, Maria Teresa Alves Martins, Bárbara Cátia Poubel, Monique Oliveira da Silva, Luiz Carlos Santana Maillot, François Schwartz, Ida Vanessa Doederlein Genes (Basel) Article Phenylketonuria (PKU) is a common inborn error of amino acid metabolism in which the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine, is functionally impaired due to pathogenic variants in the PAH gene. Thirty-four Brazilian patients with a biochemical diagnosis of PKU, from 33 unrelated families, were analyzed through next-generation sequencing in the Ion Torrent PGM™ platform. Phenotype–genotype correlations were made based on the BioPKU database. Three patients required additional Sanger sequencing analyses. Twenty-six different pathogenic variants were identified. The most frequent variants were c.1315+1G>A (n = 8/66), c.473G>A (n = 6/66), and c.1162G>A (n = 6/66). One novel variant, c.524C>G (p.Pro175Arg), was found in one allele and was predicted as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG) criteria. The molecular modeling of p.Pro175Arg indicated that this substitution can affect monomers binding in the PAH tetramer, which could lead to a change in the stability and activity of this enzyme. Next-generation sequencing was a fast and effective method for diagnosing PKU and is useful for patient phenotype prediction and genetic counseling. MDPI 2020-12-25 /pmc/articles/PMC7824641/ /pubmed/33375644 http://dx.doi.org/10.3390/genes12010020 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tresbach, Rafael Hencke
Sperb-Ludwig, Fernanda
Ligabue-Braun, Rodrigo
Tonon, Tássia
de Oliveira Cardoso, Maria Teresinha
Heredia, Romina Soledad
da Silva Rosa, Maria Teresa Alves
Martins, Bárbara Cátia
Poubel, Monique Oliveira
da Silva, Luiz Carlos Santana
Maillot, François
Schwartz, Ida Vanessa Doederlein
Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients
title Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients
title_full Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients
title_fullStr Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients
title_full_unstemmed Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients
title_short Phenylketonuria Diagnosis by Massive Parallel Sequencing and Genotype-Phenotype Association in Brazilian Patients
title_sort phenylketonuria diagnosis by massive parallel sequencing and genotype-phenotype association in brazilian patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824641/
https://www.ncbi.nlm.nih.gov/pubmed/33375644
http://dx.doi.org/10.3390/genes12010020
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