Heterozygosis for CYP21A2 mutation considered as 21-hydroxylase deficiency in neonatal screening
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , , |
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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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 |
_version_ |
1814268266992893952 |