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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7824641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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