Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening

Detalhes bibliográficos
Autor(a) principal: Soardi, Fernanda Caroline
Data de Publicação: 2008
Outros Autores: Lemos-Marini, Sofia Helena Valente de, Coeli, Fernanda Borchers, Maturana, Víctor Gonçalves, Silva, Márcia Duarte Barbosa da, Bernardi, Renan Darin, Justo, Giselle Zenker [UNIFESP], Mello, Maricilda Palandi de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://dx.doi.org/10.1590/S0004-27302008000800030
https://repositorio.unifesp.br/handle/11600/4626
Resumo: Steroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17-hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that healthy preterm infants have high levels of 17-OHP resulting in false positive cases. We report on molecular features of a boy born pre-term (GA = 30 weeks; weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon neonatal screening who was treated as having CAH up to the age of 8 months. He was brought to us for molecular diagnosis. Medication was gradually suspended and serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound heterozygous status with a group of nucleotide alterations located at the 3' end intron 4 and 5' end exon 5 corresponding to the splice site acceptor region. Molecular studies continued in order to exclude the possibility of a nonclassical 21-OHD form. The group of three nucleotide changes was demonstrated to be a normal variant since they failed to interfere with the normal splicing process upon minigene studies.
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spelling Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screeningHeterozigose para mutação no gene CYP21A2 considerada como deficiência de 21-hidroxilase na triagem neonatalNeonatal screeningMinigenes21-hydroxylase deficiencyCYP21A2 mutationsTriagem neonatalMutações CYP21A2MinigenesDeficiência de 21-hidroxilaseSteroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17-hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that healthy preterm infants have high levels of 17-OHP resulting in false positive cases. We report on molecular features of a boy born pre-term (GA = 30 weeks; weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon neonatal screening who was treated as having CAH up to the age of 8 months. He was brought to us for molecular diagnosis. Medication was gradually suspended and serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound heterozygous status with a group of nucleotide alterations located at the 3' end intron 4 and 5' end exon 5 corresponding to the splice site acceptor region. Molecular studies continued in order to exclude the possibility of a nonclassical 21-OHD form. The group of three nucleotide changes was demonstrated to be a normal variant since they failed to interfere with the normal splicing process upon minigene studies.A deficiência de 21-hidroxilase (21-OHD) é uma doença autossômica recessiva que contribui com mais de 90% dos casos de hiperplasia congênita da adrenal. O teste de dosagem de 17-hidroxiprogesterona (17-OHP) por radioimunoensaio em amostras de sangue colhidas em papel de filtro tem sido o método mais usado nos programas de triagem neonatal. No entanto, essa triagem pode apresentar alto número de falso-positivos pelo fato de os recém-nascidos prematuros apresentarem dosagens mais elevadas deste esteróide. Apresentamos aqui os estudos moleculares de uma criança, sexo masculino, nascida pré-termo (IG = 30 sem; peso = 1.390 g) que apresentava valores elevados de 17-OHP sérica (91,2 nmol/L, normal < 40) na triagem neonatal e que foi tratada como portadora da forma clássica da 21-OHD até a idade de 8 meses quando nos foi encaminhada para diagnóstico molecular. A terapia foi, então, gradativamente descontinuada, sendo que as concentrações séricas de 17-OHP se mantiveram normais. A mutação p.V281L foi encontrada em heterozigose composta com um grupo de alterações no terminal 3' do íntron 4 e no terminal 5' do éxon 5 correspondendo à região do sítio aceptor de splicing. A análise do gene CYP21A2 prosseguiu para se excluir a possibilidade de a criança ser afetada com a forma não-clássica de 21-OHD. Pela análise de minigene ficou demonstrado que o grupo de três trocas nucleotídicas não afeta o processo normal de transcrição. Concluindo, a criança é apenas heterozigota da mutação p.V281L sem necessidade de tratamento.Universidade Estadual de Campinas Centro de Biologia Molecular e Engenharia GenéticaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Pediatria e Centro de Investigação em PediatriaUniversidade Federal de São Paulo (UNIFESP) Departamento de Bioquímica Disciplina de Biologia MolecularUNIFESP, Depto. de Bioquímica Disciplina de Biologia MolecularSciELOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Sociedade Brasileira de Endocrinologia e MetabologiaUniversidade Estadual de Campinas (UNICAMP)Universidade Federal de São Paulo (UNIFESP)Soardi, Fernanda CarolineLemos-Marini, Sofia Helena Valente deCoeli, Fernanda BorchersMaturana, Víctor GonçalvesSilva, Márcia Duarte Barbosa daBernardi, Renan DarinJusto, Giselle Zenker [UNIFESP]Mello, Maricilda Palandi de2015-06-14T13:38:48Z2015-06-14T13:38:48Z2008-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion1388-1392application/pdfhttps://dx.doi.org/10.1590/S0004-27302008000800030Arquivos Brasileiros de Endocrinologia & Metabologia. Sociedade Brasileira de Endocrinologia e Metabologia, v. 52, n. 8, p. 1388-1392, 2008.10.1590/S0004-27302008000800030S0004-27302008000800030.pdf0004-2730S0004-27302008000800030https://repositorio.unifesp.br/handle/11600/4626WOS:000262313500030engArquivos Brasileiros de Endocrinologia & Metabologiainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-28T15:59:37Zoai:repositorio.unifesp.br/:11600/4626Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-07-28T15:59:37Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
Heterozigose para mutação no gene CYP21A2 considerada como deficiência de 21-hidroxilase na triagem neonatal
title Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
spellingShingle Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
Soardi, Fernanda Caroline
Neonatal screening
Minigenes
21-hydroxylase deficiency
CYP21A2 mutations
Triagem neonatal
Mutações CYP21A2
Minigenes
Deficiência de 21-hidroxilase
title_short Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
title_full Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
title_fullStr Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
title_full_unstemmed Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
title_sort Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
author Soardi, Fernanda Caroline
author_facet Soardi, Fernanda Caroline
Lemos-Marini, Sofia Helena Valente de
Coeli, Fernanda Borchers
Maturana, Víctor Gonçalves
Silva, Márcia Duarte Barbosa da
Bernardi, Renan Darin
Justo, Giselle Zenker [UNIFESP]
Mello, Maricilda Palandi de
author_role author
author2 Lemos-Marini, Sofia Helena Valente de
Coeli, Fernanda Borchers
Maturana, Víctor Gonçalves
Silva, Márcia Duarte Barbosa da
Bernardi, Renan Darin
Justo, Giselle Zenker [UNIFESP]
Mello, Maricilda Palandi de
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Soardi, Fernanda Caroline
Lemos-Marini, Sofia Helena Valente de
Coeli, Fernanda Borchers
Maturana, Víctor Gonçalves
Silva, Márcia Duarte Barbosa da
Bernardi, Renan Darin
Justo, Giselle Zenker [UNIFESP]
Mello, Maricilda Palandi de
dc.subject.por.fl_str_mv Neonatal screening
Minigenes
21-hydroxylase deficiency
CYP21A2 mutations
Triagem neonatal
Mutações CYP21A2
Minigenes
Deficiência de 21-hidroxilase
topic Neonatal screening
Minigenes
21-hydroxylase deficiency
CYP21A2 mutations
Triagem neonatal
Mutações CYP21A2
Minigenes
Deficiência de 21-hidroxilase
description Steroid 21-hydroxylase deficiency (21-OHD) accounts for more than 90% of congenital adrenal hyperplasia. CAH newborn screening, in general, is based on 17-hydroxyprogesterone dosage (17-OHP), however it is complicated by the fact that healthy preterm infants have high levels of 17-OHP resulting in false positive cases. We report on molecular features of a boy born pre-term (GA = 30 weeks; weight = 1,390 g) with elevated levels of 17-OHP (91.2 nmol/L, normal < 40) upon neonatal screening who was treated as having CAH up to the age of 8 months. He was brought to us for molecular diagnosis. Medication was gradually suspended and serum 17-OHP dosages mantained normal. The p.V281L mutation was found in compound heterozygous status with a group of nucleotide alterations located at the 3' end intron 4 and 5' end exon 5 corresponding to the splice site acceptor region. Molecular studies continued in order to exclude the possibility of a nonclassical 21-OHD form. The group of three nucleotide changes was demonstrated to be a normal variant since they failed to interfere with the normal splicing process upon minigene studies.
publishDate 2008
dc.date.none.fl_str_mv 2008-11-01
2015-06-14T13:38:48Z
2015-06-14T13:38:48Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://dx.doi.org/10.1590/S0004-27302008000800030
Arquivos Brasileiros de Endocrinologia & Metabologia. Sociedade Brasileira de Endocrinologia e Metabologia, v. 52, n. 8, p. 1388-1392, 2008.
10.1590/S0004-27302008000800030
S0004-27302008000800030.pdf
0004-2730
S0004-27302008000800030
https://repositorio.unifesp.br/handle/11600/4626
WOS:000262313500030
url https://dx.doi.org/10.1590/S0004-27302008000800030
https://repositorio.unifesp.br/handle/11600/4626
identifier_str_mv Arquivos Brasileiros de Endocrinologia & Metabologia. Sociedade Brasileira de Endocrinologia e Metabologia, v. 52, n. 8, p. 1388-1392, 2008.
10.1590/S0004-27302008000800030
S0004-27302008000800030.pdf
0004-2730
S0004-27302008000800030
WOS:000262313500030
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Arquivos Brasileiros de Endocrinologia & Metabologia
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1388-1392
application/pdf
dc.publisher.none.fl_str_mv Sociedade Brasileira de Endocrinologia e Metabologia
publisher.none.fl_str_mv Sociedade Brasileira de Endocrinologia e Metabologia
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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