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IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO

OBJECTIVE: To identify phenylalanine hydroxylase (PAH) mutations in patients with phenylketonuria (PKU) from the Newborn Screening Service in Mato Grosso, Midwest Brazil. METHODS: This is a cross-sectional descriptive study. The sample consisted of 19 PKU patients diagnosed by newborn screening. Mol...

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Autores principales: Costa, Roseli Divino, Galera, Bianca Borsatto, Rezende, Bianca Costa, Venâncio, Amanda Cristina, Galera, Marcial Francis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade de Pediatria de São Paulo 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025444/
https://www.ncbi.nlm.nih.gov/pubmed/32074228
http://dx.doi.org/10.1590/1984-0462/2020/38/2018351
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author Costa, Roseli Divino
Galera, Bianca Borsatto
Rezende, Bianca Costa
Venâncio, Amanda Cristina
Galera, Marcial Francis
author_facet Costa, Roseli Divino
Galera, Bianca Borsatto
Rezende, Bianca Costa
Venâncio, Amanda Cristina
Galera, Marcial Francis
author_sort Costa, Roseli Divino
collection PubMed
description OBJECTIVE: To identify phenylalanine hydroxylase (PAH) mutations in patients with phenylketonuria (PKU) from the Newborn Screening Service in Mato Grosso, Midwest Brazil. METHODS: This is a cross-sectional descriptive study. The sample consisted of 19 PKU patients diagnosed by newborn screening. Molecular analysis: DNA extraction using the “salting-out” method. Detection of IVS10nt-11G>A, V388M, R261Q, R261X, R252W, and R408W mutations by the restriction fragment length polymorphism (RFLP) technique. RESULTS: Two mutant alleles were identified in four patients (21.1%), one allele in five patients (26.2%), and none in the remaining ten patients (52.6%). A total of 13/38 alleles were detected, corresponding to 34.2% of the PAH alleles present. The most prevalent variant was V388M (13.2% of the alleles), followed by R261Q (10.1%) and IVS10nt-11G>A (7.9%). Three variants (R261X, R252W, and R408W) were not found. The most frequent mutation types were: missense mutation in eight alleles (18.4%) and splicing in four alleles (10.5%). The model proposed by Guldberg to determine a genotype/phenotype correlation was applied to four classical PKU patients with two identified mutations. In three of them, the predicted moderate/moderate or moderate PKU phenotype did not coincide with the actual diagnosis. The prediction coincided with the diagnosis of one classic PKU patient. The estimated incidence of PKU for Mato Grosso, Brazil, was 1:33,342 live births from 2003 to 2015. CONCLUSION: The only mutations found in the analyzed samples were the IVS10nt-11G>A, V388M, and R261Q. The genotype/phenotype correlation only occurred in four (5.3%) patients.
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spelling pubmed-70254442020-02-27 IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO Costa, Roseli Divino Galera, Bianca Borsatto Rezende, Bianca Costa Venâncio, Amanda Cristina Galera, Marcial Francis Rev Paul Pediatr Original Article OBJECTIVE: To identify phenylalanine hydroxylase (PAH) mutations in patients with phenylketonuria (PKU) from the Newborn Screening Service in Mato Grosso, Midwest Brazil. METHODS: This is a cross-sectional descriptive study. The sample consisted of 19 PKU patients diagnosed by newborn screening. Molecular analysis: DNA extraction using the “salting-out” method. Detection of IVS10nt-11G>A, V388M, R261Q, R261X, R252W, and R408W mutations by the restriction fragment length polymorphism (RFLP) technique. RESULTS: Two mutant alleles were identified in four patients (21.1%), one allele in five patients (26.2%), and none in the remaining ten patients (52.6%). A total of 13/38 alleles were detected, corresponding to 34.2% of the PAH alleles present. The most prevalent variant was V388M (13.2% of the alleles), followed by R261Q (10.1%) and IVS10nt-11G>A (7.9%). Three variants (R261X, R252W, and R408W) were not found. The most frequent mutation types were: missense mutation in eight alleles (18.4%) and splicing in four alleles (10.5%). The model proposed by Guldberg to determine a genotype/phenotype correlation was applied to four classical PKU patients with two identified mutations. In three of them, the predicted moderate/moderate or moderate PKU phenotype did not coincide with the actual diagnosis. The prediction coincided with the diagnosis of one classic PKU patient. The estimated incidence of PKU for Mato Grosso, Brazil, was 1:33,342 live births from 2003 to 2015. CONCLUSION: The only mutations found in the analyzed samples were the IVS10nt-11G>A, V388M, and R261Q. The genotype/phenotype correlation only occurred in four (5.3%) patients. Sociedade de Pediatria de São Paulo 2020-02-14 /pmc/articles/PMC7025444/ /pubmed/32074228 http://dx.doi.org/10.1590/1984-0462/2020/38/2018351 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License
spellingShingle Original Article
Costa, Roseli Divino
Galera, Bianca Borsatto
Rezende, Bianca Costa
Venâncio, Amanda Cristina
Galera, Marcial Francis
IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO
title IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO
title_full IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO
title_fullStr IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO
title_full_unstemmed IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO
title_short IDENTIFICATION OF MUTATIONS IN THE PAH GENE IN PKU PATIENTS IN THE STATE OF MATO GROSSO
title_sort identification of mutations in the pah gene in pku patients in the state of mato grosso
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025444/
https://www.ncbi.nlm.nih.gov/pubmed/32074228
http://dx.doi.org/10.1590/1984-0462/2020/38/2018351
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