Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/6851 |
Resumo: | 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. |
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Freitas, Pedro Eduardo BonfimAndrade, Roseani SSantos, Ândrea K. Ribeiro dosSilva, Luiz C. Santana da2023-07-18T13:49:03Z2023-07-18T13:49:03Z2023FREITAS, Pedro Eduardo Bonfim et al. Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para. Molecular Genetics and Genomic Medicine, v. 8, e2224, 2023. DOI: https://doi.org/10.1002/mgg3.2224. Disponível em: https://onlinelibrary.wiley.com/doi/epdf/10.1002/mgg3.22242324-9269https://patua.iec.gov.br/handle/iec/685110.1002/mgg3.2224Background: 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.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.engWileyMolecular characterization of phenylketonuria patients from the North Region of Brazil: State of Parainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFenilcetonúria Materna / genéticaGenótipoFenótipoAnálise CitogenéticaMutação / genéticainfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALMolecular characterization of phenylketonuria patients from the North Region.pdfMolecular characterization of phenylketonuria patients from the North Region.pdfapplication/pdf511307https://patua.iec.gov.br/bitstreams/11d93f35-5620-449d-a4e1-d2db4e90981e/download184b0d4d689d7b460939c458611fe76aMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/0ba72863-d382-4d66-8dfd-04f06252b44f/download11832eea31b16df8613079d742d61793MD52TEXTMolecular characterization of phenylketonuria patients from the North Region.pdf.txtMolecular characterization of phenylketonuria patients from the North Region.pdf.txtExtracted texttext/plain52050https://patua.iec.gov.br/bitstreams/2d3b1137-a85e-4666-b69e-178e8281c3d1/download4d7010bc1cf87d58649090b54d400fb3MD53THUMBNAILMolecular characterization of phenylketonuria patients from the North Region.pdf.jpgMolecular characterization of phenylketonuria patients from the North Region.pdf.jpgGenerated Thumbnailimage/jpeg5972https://patua.iec.gov.br/bitstreams/8e48afe1-2c0d-4def-aef6-3c72f5e9a131/download22565d26592eac98ecc7e6da1dddb417MD54iec/68512023-07-18 14:19:02.842oai:patua.iec.gov.br:iec/6851https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2023-07-18T14:19:02Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falsePGI+TGljZW7Dp2EgZGUgRGlzdHJpYnVpw6fDo28gTsOjbyBFeGNsdXNpdmE8L2I+DQoNClRvZG8gZGVwb3NpdGFudGUgZGUgbWF0ZXJpYWwgbm8gUGF0dcOhIGRldmUgY29uY2VkZXIgYW8gSW5zdGl0dXRvIEV2YW5kcm8gQ2hhZ2FzIHVtYSBMaWNlbsOnYSBkZSBEaXN0cmlidWnDp8OjbyBOw6NvIEV4Y2x1c2l2YSBwYXJhIHRvcm5hciBlIG1hbnRlciBhY2Vzc8OtdmVpcyBvcyBzZXVzIGRvY3VtZW50b3MgZW0gZm9ybWF0byBkaWdpdGFsLiANCg0KQ29tIGEgY29uY2Vzc8OjbyBkZXNzYSBsaWNlbsOnYSBuw6NvIGV4Y2x1c2l2YSwgbyBkZXBvc2l0YW50ZSBjb250aW51YSBhIHJldGVyIHRvZG9zIG9zIGRpcmVpdG9zIGRlIGF1dG9yLg0KDQpBbyBhc3NpbmFyIGUgZW50cmVnYXIgZXN0YSBsaWNlbsOnYSB2b2PDqiAoYXV0b3Igb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzKQ0KDQphKSBEZWNsYXJhIHF1ZSBjb25oZWNlIGEgcG9sw610aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRlIHNldSBkb2N1bWVudG8uDQoNCmIpIENvbmNlZGUgYW8gSW5zdGl0dXRvIEV2YW5kcm8gQ2hhZ2FzIG8gZGlyZWl0byBuw6NvIGV4Y2x1c2l2byBkZSBhcnF1aXZhciwgcmVwcm9kdXppciwgY29udmVydGVyIChjb21vIGRlZmluaWRvIGEgc2VndWlyKSwgY29tdW5pY2FyIGUvb3UgZGlzdHJpYnVpciBubyA8Yj5QYXR1w6E8L2I+LCBvIGRvY3VtZW50byBlbnRyZWd1ZSAoaW5jbHVpbmRvIG8gcmVzdW1vL2Fic3RyYWN0KSBlbSBmb3JtYXRvIGRpZ2l0YWwgb3UgcG9yIHF1YWxxdWVyIG91dHJvIG1laW8uDQoNCmMpIERlY2xhcmEgcXVlIGF1dG9yaXphIG8gSW5zdGl0dXRvIEV2YW5kcm8gQ2hhZ2FzIGEgYXJxdWl2YXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlc3NlIGRvY3VtZW50byBlIGNvbnZlcnTDqi1sbywgc2VtIGFsdGVyYXIgbyBzZXUgY29udGXDumRvLCBwYXJhIHF1YWxxdWVyIGZvcm1hdG8gZGUgZmljaGVpcm8sIG1laW8gb3Ugc3Vwb3J0ZSwgcGFyYSBlZmVpdG9zIGRlIHNlZ3VyYW7Dp2EsIHByZXNlcnZhw6fDo28gKGJhY2t1cCkgZSBhY2Vzc28uDQoNCmQpIERlY2xhcmEgcXVlIG8gZG9jdW1lbnRvIHN1Ym1ldGlkbyDDqSBvIHNldSB0cmFiYWxobyBvcmlnaW5hbCBlIHF1ZSBkZXTDqW0gbyBkaXJlaXRvIGRlIGNvbmNlZGVyIGEgdGVyY2Vpcm9zIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGEgZW50cmVnYSBkbyBkb2N1bWVudG8gbsOjbyBpbmZyaW5nZSBvcyBkaXJlaXRvcyBkZSBxdWFscXVlciBvdXRyYSBwZXNzb2Egb3UgZW50aWRhZGUuDQoNCmUpIERlY2xhcmEgcXVlLCBubyBjYXNvIGRvIGRvY3VtZW50byBzdWJtZXRpZG8gY29udGVyIG1hdGVyaWFsIGRvIHF1YWwgbsOjbyBkZXTDqW0gb3MgZGlyZWl0b3MgZGUgYXV0b3IsIG9idGV2ZSBhIGF1dG9yaXphw6fDo28gaXJyZXN0cml0YSBkbyByZXNwZWN0aXZvIGRldGVudG9yIGRlc3NlcyBkaXJlaXRvcywgcGFyYSBjZWRlciBhbyBJbnN0aXR1dG8gRXZhbmRybyBDaGFnYXMgb3MgZGlyZWl0b3MgcmVxdWVyaWRvcyBwb3IgZXN0YSBMaWNlbsOnYSBlIGF1dG9yaXphciBhIHV0aWxpesOhLWxvcyBsZWdhbG1lbnRlLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGVzc2UgbWF0ZXJpYWwgY3Vqb3MgZGlyZWl0b3Mgc8OjbyBkZSB0ZXJjZWlyb3MgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBjb250ZcO6ZG8gZG8gZG9jdW1lbnRvIGVudHJlZ3VlLg0KDQpmKSBTRSBPIERPQ1VNRU5UTyBFTlRSRUdVRSBGT1IgQkFTRUFETyBFTSBUUkFCQUxITyBGSU5BTkNJQURPIE9VIEFQT0lBRE8gUE9SIE9VVFJBIElOU1RJVFVJw4fDg08gUVVFIE7Dg08gTyBJTlNUSVRVVE8gRVZBTkRSTyBDSEFHQVMsIERFQ0xBUkEgUVVFIENVTVBSSVUgUVVBSVNRVUVSIE9CUklHQcOHw5VFUyBFWElHSURBUyBQRUxPIFJFU1BFQ1RJVk8gQ09OVFJBVE8gT1UgQUNPUkRPLg0KDQpPIEluc3RpdHV0byBFdmFuZHJvIENoYWdhcyBpZGVudGlmaWNhcsOhIGNsYXJhbWVudGUgbyhzKSBub21lKHMpIGRvKHMpIGF1dG9yKGVzKSBkb3MgZGlyZWl0b3MgZG8gZG9jdW1lbnRvIGVudHJlZ3VlIGUgbsOjbyBmYXLDoSBxdWFscXVlciBhbHRlcmHDp8OjbyBhbMOpbSBkbyBwcmV2aXN0byBuYSBhbMOtbmVhIGIpLg== |
dc.title.pt_BR.fl_str_mv |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
title |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
spellingShingle |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para Freitas, Pedro Eduardo Bonfim Fenilcetonúria Materna / genética Genótipo Fenótipo Análise Citogenética Mutação / genética |
title_short |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
title_full |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
title_fullStr |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
title_full_unstemmed |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
title_sort |
Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para |
author |
Freitas, Pedro Eduardo Bonfim |
author_facet |
Freitas, Pedro Eduardo Bonfim Andrade, Roseani S Santos, Ândrea K. Ribeiro dos Silva, Luiz C. Santana da |
author_role |
author |
author2 |
Andrade, Roseani S Santos, Ândrea K. Ribeiro dos Silva, Luiz C. Santana da |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Freitas, Pedro Eduardo Bonfim Andrade, Roseani S Santos, Ândrea K. Ribeiro dos Silva, Luiz C. Santana da |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Fenilcetonúria Materna / genética Genótipo Fenótipo Análise Citogenética Mutação / genética |
topic |
Fenilcetonúria Materna / genética Genótipo Fenótipo Análise Citogenética Mutação / genética |
description |
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. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-07-18T13:49:03Z |
dc.date.available.fl_str_mv |
2023-07-18T13:49:03Z |
dc.date.issued.fl_str_mv |
2023 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
FREITAS, Pedro Eduardo Bonfim et al. Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para. Molecular Genetics and Genomic Medicine, v. 8, e2224, 2023. DOI: https://doi.org/10.1002/mgg3.2224. Disponível em: https://onlinelibrary.wiley.com/doi/epdf/10.1002/mgg3.2224 |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/6851 |
dc.identifier.issn.-.fl_str_mv |
2324-9269 |
dc.identifier.doi.pt_BR.fl_str_mv |
10.1002/mgg3.2224 |
identifier_str_mv |
FREITAS, Pedro Eduardo Bonfim et al. Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Para. Molecular Genetics and Genomic Medicine, v. 8, e2224, 2023. DOI: https://doi.org/10.1002/mgg3.2224. Disponível em: https://onlinelibrary.wiley.com/doi/epdf/10.1002/mgg3.2224 2324-9269 10.1002/mgg3.2224 |
url |
https://patua.iec.gov.br/handle/iec/6851 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Digital do Instituto Evandro Chagas (Patuá) instname:Instituto Evandro Chagas (IEC) instacron:IEC |
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Instituto Evandro Chagas (IEC) |
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IEC |
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