Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMT |
Texto Completo: | http://ri.ufmt.br/handle/1/4358 |
Resumo: | Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. The classic form is caused by the deficiency in the enzyme phenylalanine hydroxylase (PAH) which catalyzes the hydroxylation of phenylalanine to tyrosine. Phenylketonuria (PKU) is detected and treated in Brazil at the National Newborn Screening Reference Services present in all Brazilian states. We tested for the IVS10nt-11G>A, V388M, R261Q, R261X, R252W and R408W mutations of the PAH gene in a sample of 19 patients being treated for PKU at the Newborn Screening Reference Service for the State of Mato Grosso. This study is crosssectional and descriptive and the 19 PKU patients in the study were detected over a 12 year period of newborn screening (2003 – 2015). Polymerase chain reaction (PCR) and specific restriction enzymes digestion were the techniques applied for the molecular analysis. Among the 19 patients that participated in this study 4 (21.1%) had two alleles identified; 5 (26.21%) patients had only one allele identified, and 10 (52.6%) were not found to have anyone of these six mutations. It was possible to identify 13/38 alleles, corresponding to 34.21% of the PAH alleles in the sample. The most prevalent mutation was V388M (13.2% of the alleles) followed by R261Q (10.1%) and IVS10nt-G>A (7.9%). Mutations R261X, R252W and R408W were not found. The most frequent types of mutations were missense, in 8 patients (18.4%) and splice in 4 patients (10.52%). Applying the model proposed by Guldberg et al. (1998), a genotype/phenotype correlation was obtained for the 4 patients with two identified mutations, all of whom had classic phenylketonuria. The predicted phenotype was moderate/mild or moderate PKU for 3 of these 4 classical PKU patients and the prediction coincided with the diagnosis of classic PKU in only 1 patient. The incidence of PKU for the State of Mato Grosso for the period from 2003 to 2015 was estimated to be 1:33,342 live births. The average coverage of the Newborn Screening Reference Service program for the State of Mato Grosso for this same period was 75.2% of all newborns. The mutations identified in this study were also found in several Brazilian studies, however, at a lower frequency than previously published data. |
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Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato GrossoFenilcetonúriaMutaçõesTriagem neonatalMato GrossoCNPQ::CIENCIAS DA SAUDEPhenylketonuriaMutationNeonatal screeningMato GrossoPhenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. The classic form is caused by the deficiency in the enzyme phenylalanine hydroxylase (PAH) which catalyzes the hydroxylation of phenylalanine to tyrosine. Phenylketonuria (PKU) is detected and treated in Brazil at the National Newborn Screening Reference Services present in all Brazilian states. We tested for the IVS10nt-11G>A, V388M, R261Q, R261X, R252W and R408W mutations of the PAH gene in a sample of 19 patients being treated for PKU at the Newborn Screening Reference Service for the State of Mato Grosso. This study is crosssectional and descriptive and the 19 PKU patients in the study were detected over a 12 year period of newborn screening (2003 – 2015). Polymerase chain reaction (PCR) and specific restriction enzymes digestion were the techniques applied for the molecular analysis. Among the 19 patients that participated in this study 4 (21.1%) had two alleles identified; 5 (26.21%) patients had only one allele identified, and 10 (52.6%) were not found to have anyone of these six mutations. It was possible to identify 13/38 alleles, corresponding to 34.21% of the PAH alleles in the sample. The most prevalent mutation was V388M (13.2% of the alleles) followed by R261Q (10.1%) and IVS10nt-G>A (7.9%). Mutations R261X, R252W and R408W were not found. The most frequent types of mutations were missense, in 8 patients (18.4%) and splice in 4 patients (10.52%). Applying the model proposed by Guldberg et al. (1998), a genotype/phenotype correlation was obtained for the 4 patients with two identified mutations, all of whom had classic phenylketonuria. The predicted phenotype was moderate/mild or moderate PKU for 3 of these 4 classical PKU patients and the prediction coincided with the diagnosis of classic PKU in only 1 patient. The incidence of PKU for the State of Mato Grosso for the period from 2003 to 2015 was estimated to be 1:33,342 live births. The average coverage of the Newborn Screening Reference Service program for the State of Mato Grosso for this same period was 75.2% of all newborns. The mutations identified in this study were also found in several Brazilian studies, however, at a lower frequency than previously published data.Fenilcetonúria (PKU) é um erro inato do metabolismo, autossômico rescessivo. A forma clássica é causada pela deficiência na enzima fenilalanina hidroxilase (PAH) que catalisa a hidroxilação de fenilalanina em tirosina. A fenilcetonúria (PKU) é detectada e tratada no Brasil nos Serviços de Referência em Triagem Neonatal, presente em todos os estados brasileiros. Este estudo é transversal e descritivo e os 19 pacientes com PKU no estudo foram detectados durante um período de 12 anos de triagem neonatal (2003-2015). Testamos as variantes IVS10nt-11G>A, V388M, R261Q, R261X, R252W e R408W do gene PAH em uma amostra de 19 pacientes tratados para PKU no Serviço de Referência em Triagem Neonatal do Estado de Mato Grosso. A reação em cadeia da polimerase (PCR) e a digestão das enzimas de restrição específicas foram às técnicas aplicadas para a análise molecular. Entre os 19 pacientes que participaram deste estudo, 4 (21,1%) tiveram dois alelos identificados; 5 (26,21%) pacientes tinham apenas um alelo identificado, e 10 (52,6%) não encontramos nenhuma dessas seis mutações. Foi possível identificar alelos de 13/38, correspondendo a 34,21% dos alelos PAH na amostra. A variante mais prevalente foi V388M (13,2% dos alelos) seguida de R261Q (10,1%) e IVS10nt-G>A (7,9%). Mutações R261X, R252W e R408W não foram encontradas. Os tipos mais frequentes de mutações foram troca de sentido, em 8 pacientes (18,4%) e de emenda em 4 pacientes (10,52%). Aplicando o modelo proposto por Guldberg et al. (1998), foi obtida uma correlação genótipo/fenótipo para os 4 pacientes com duas mutações identificadas, todas com fenilcetonúria clássica. O fenótipo previsto foi de PKU moderada/moderada ou moderada para 3 desses 4 pacientes clássicos de PKU e a predição coincidiu com o diagnóstico de PKU clássica em apenas 1 paciente. A incidência de PKU para o Estado de Mato Grosso para o período de 2003 a 2015 foi estimada em 1: 33.342 NV. A cobertura média do programa do Serviço de Referência de Triagem Neonatal para o Estado de Mato Grosso para este mesmo período foi de 75,2% de todos os recém-nascidos. As mutações identificadas neste estudo também foram encontradas em vários estudos brasileiros, porém, em menor frequência do que os dados publicados anteriormente.Universidade Federal de Mato GrossoBrasilFaculdade de Medicina (FM)UFMT CUC - CuiabáPrograma de Pós-Graduação em Ciências da SaúdeGalera, Marcial Francishttp://lattes.cnpq.br/3408657282738863Galera, Marcial Francis404.138.021-91http://lattes.cnpq.br/3408657282738863Ferreira, Maria de Fátima de Carvalho729.816.017-68http://lattes.cnpq.br/1416048337560983404.138.021-91Perez, Ana Beatriz Alvarez047.866.698-57http://lattes.cnpq.br/4784102068388854Costa, Roseli Divino2023-06-26T17:01:18Z2017-11-152023-06-26T17:01:18Z2017-08-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCOSTA, Roseli Divino. Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso. 2017. 65 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Mato Grosso, Faculdade de Medicina, Cuiabá, 2017.http://ri.ufmt.br/handle/1/4358porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMTinstname:Universidade Federal de Mato Grosso (UFMT)instacron:UFMT2023-07-01T07:03:05Zoai:localhost:1/4358Repositório InstitucionalPUBhttp://ri.ufmt.br/oai/requestjordanbiblio@gmail.comopendoar:2023-07-01T07:03:05Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT)false |
dc.title.none.fl_str_mv |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
title |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
spellingShingle |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso Costa, Roseli Divino Fenilcetonúria Mutações Triagem neonatal Mato Grosso CNPQ::CIENCIAS DA SAUDE Phenylketonuria Mutation Neonatal screening Mato Grosso |
title_short |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
title_full |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
title_fullStr |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
title_full_unstemmed |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
title_sort |
Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso |
author |
Costa, Roseli Divino |
author_facet |
Costa, Roseli Divino |
author_role |
author |
dc.contributor.none.fl_str_mv |
Galera, Marcial Francis http://lattes.cnpq.br/3408657282738863 Galera, Marcial Francis 404.138.021-91 http://lattes.cnpq.br/3408657282738863 Ferreira, Maria de Fátima de Carvalho 729.816.017-68 http://lattes.cnpq.br/1416048337560983 404.138.021-91 Perez, Ana Beatriz Alvarez 047.866.698-57 http://lattes.cnpq.br/4784102068388854 |
dc.contributor.author.fl_str_mv |
Costa, Roseli Divino |
dc.subject.por.fl_str_mv |
Fenilcetonúria Mutações Triagem neonatal Mato Grosso CNPQ::CIENCIAS DA SAUDE Phenylketonuria Mutation Neonatal screening Mato Grosso |
topic |
Fenilcetonúria Mutações Triagem neonatal Mato Grosso CNPQ::CIENCIAS DA SAUDE Phenylketonuria Mutation Neonatal screening Mato Grosso |
description |
Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism. The classic form is caused by the deficiency in the enzyme phenylalanine hydroxylase (PAH) which catalyzes the hydroxylation of phenylalanine to tyrosine. Phenylketonuria (PKU) is detected and treated in Brazil at the National Newborn Screening Reference Services present in all Brazilian states. We tested for the IVS10nt-11G>A, V388M, R261Q, R261X, R252W and R408W mutations of the PAH gene in a sample of 19 patients being treated for PKU at the Newborn Screening Reference Service for the State of Mato Grosso. This study is crosssectional and descriptive and the 19 PKU patients in the study were detected over a 12 year period of newborn screening (2003 – 2015). Polymerase chain reaction (PCR) and specific restriction enzymes digestion were the techniques applied for the molecular analysis. Among the 19 patients that participated in this study 4 (21.1%) had two alleles identified; 5 (26.21%) patients had only one allele identified, and 10 (52.6%) were not found to have anyone of these six mutations. It was possible to identify 13/38 alleles, corresponding to 34.21% of the PAH alleles in the sample. The most prevalent mutation was V388M (13.2% of the alleles) followed by R261Q (10.1%) and IVS10nt-G>A (7.9%). Mutations R261X, R252W and R408W were not found. The most frequent types of mutations were missense, in 8 patients (18.4%) and splice in 4 patients (10.52%). Applying the model proposed by Guldberg et al. (1998), a genotype/phenotype correlation was obtained for the 4 patients with two identified mutations, all of whom had classic phenylketonuria. The predicted phenotype was moderate/mild or moderate PKU for 3 of these 4 classical PKU patients and the prediction coincided with the diagnosis of classic PKU in only 1 patient. The incidence of PKU for the State of Mato Grosso for the period from 2003 to 2015 was estimated to be 1:33,342 live births. The average coverage of the Newborn Screening Reference Service program for the State of Mato Grosso for this same period was 75.2% of all newborns. The mutations identified in this study were also found in several Brazilian studies, however, at a lower frequency than previously published data. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-11-15 2017-08-29 2023-06-26T17:01:18Z 2023-06-26T17:01:18Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
COSTA, Roseli Divino. Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso. 2017. 65 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Mato Grosso, Faculdade de Medicina, Cuiabá, 2017. http://ri.ufmt.br/handle/1/4358 |
identifier_str_mv |
COSTA, Roseli Divino. Estudo das mutações IVS10NT-11G>A, V388M, R261Q, R261X, R252W E R408W no gene da fenilalanina hidroxilase em pacientes com fenilcetonúria do estado de Mato Grosso. 2017. 65 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Mato Grosso, Faculdade de Medicina, Cuiabá, 2017. |
url |
http://ri.ufmt.br/handle/1/4358 |
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por |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de Mato Grosso Brasil Faculdade de Medicina (FM) UFMT CUC - Cuiabá Programa de Pós-Graduação em Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Mato Grosso Brasil Faculdade de Medicina (FM) UFMT CUC - Cuiabá Programa de Pós-Graduação em Ciências da Saúde |
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reponame:Repositório Institucional da UFMT instname:Universidade Federal de Mato Grosso (UFMT) instacron:UFMT |
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Universidade Federal de Mato Grosso (UFMT) |
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Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT) |
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jordanbiblio@gmail.com |
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