In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia

Detalhes bibliográficos
Autor(a) principal: Soardi, Fernanda Caroline, 1980-
Data de Publicação: 2014
Outros Autores: Mello, Maricilda Palandi de, 1954-
Tipo de documento: Artigo
Título da fonte: Repositório da Produção Científica e Intelectual da Unicamp
Texto Completo: https://hdl.handle.net/20.500.12733/355
Resumo: Agradecimentos: This study was supported by Karolinska Institutet, Stockholm County Council, The Marianne and Marcus Wallenberg Foundation, Stiftelsen Frimurare Barnhuset, Sallskapet Barnavard, the Soderberg Foundation, the Novo Nordisk Foundation and the Swedish Research Council (Project No. 12198 to A.W.). F.C.S. was supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasil (CAPES Grant No. 1919-5)
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spelling In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasiaHiperplasia suprarrenal congênitaGenética molecularAdrenal hyperplasia, CongenitalMolecular genetics.Artigo originalAgradecimentos: This study was supported by Karolinska Institutet, Stockholm County Council, The Marianne and Marcus Wallenberg Foundation, Stiftelsen Frimurare Barnhuset, Sallskapet Barnavard, the Soderberg Foundation, the Novo Nordisk Foundation and the Swedish Research Council (Project No. 12198 to A.W.). F.C.S. was supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasil (CAPES Grant No. 1919-5)Abstract: A detailed genotype-phenotype evaluation is presented by studying the enzyme activities of five rare amino acid substitutions (Arg233Gly, Ala265Ser, Arg341Trp, Arg366Cys and Met473Ile) identified in the CYP21A2 gene in patients investigated for Congenital adrenal hyperplasia (CAH). To investigate whether the mutations identified in the CYP21A2 gene are disease causing and to establish a gradient for the degree of enzyme impairment to improve prediction of patient phenotype. The CYP21A2 genes of seven patients investigated for CAH were sequenced and five mutations were identified. The mutant proteins were expressed in vitro in COS-1 cells, and the enzyme activities towards the two natural substrates were determined to verify the disease-causing state of the mutations. The in vitro activities of these rare mutations were also compared with the activities of four mutations known to cause nonclassic CAH (Pro30Leu, Val281Leu, Pro453Ser and Pro482Ser) in addition to an in silico structural evaluation of the novel mutants. To verify the disease-causing state of novel mutations. Five CYP21A2 mutations were identified (Arg233Gly, Ala265Ser, Arg341Trp, Arg366Cys and Met473Ile). All mutant proteins exhibited enzyme activities above 5%, and four mutations were classified as nonclassic and one as a normal variant. By comparing the investigated protein changes with four common mutations causing nonclassic CAH, a gradient for the degree of enzyme impairment could be established. Studying rare mutations in CAH increases our knowledge regarding the molecular mechanisms that render a mutation pathogenic. It also improves phenotype predictions and genetic counselling for future generationsCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFechadoUNIVERSIDADE ESTADUAL DE CAMPINASSoardi, Fernanda Caroline, 1980-Mello, Maricilda Palandi de, 1954-2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12733/355SOARDI, Fernanda Caroline; MELLO, Maricilda Palandi de. In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia. Clinical endocrinology. Chichester : Wiley, 2014. Vol. 82, n. 1 (Jan., 2014), p. 37-44. Disponível em: https://hdl.handle.net/20.500.12733/355. Acesso em: 24 mai. 2023.Inglêshttps://repositorio.unicamp.br/acervo/detalhe/1231404reponame:Repositório da Produção Científica e Intelectual da Unicampinstname:Universidade Estadual de Campinas (UNICAMP)instacron:UNICAMPinfo:eu-repo/semantics/openAccess2021-11-11T11:07:50Zoai:https://www.repositorio.unicamp.br/:1231404Repositório InstitucionalPUBhttp://repositorio.unicamp.br/oai/requestreposip@unicamp.bropendoar:2021-11-11T11:07:50Repositório da Produção Científica e Intelectual da Unicamp - Universidade Estadual de Campinas (UNICAMP)false
dc.title.none.fl_str_mv In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
title In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
spellingShingle In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
Soardi, Fernanda Caroline, 1980-
Hiperplasia suprarrenal congênita
Genética molecular
Adrenal hyperplasia, Congenital
Molecular genetics.
Artigo original
title_short In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
title_full In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
title_fullStr In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
title_full_unstemmed In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
title_sort In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
author Soardi, Fernanda Caroline, 1980-
author_facet Soardi, Fernanda Caroline, 1980-
Mello, Maricilda Palandi de, 1954-
author_role author
author2 Mello, Maricilda Palandi de, 1954-
author2_role author
dc.contributor.none.fl_str_mv UNIVERSIDADE ESTADUAL DE CAMPINAS
dc.contributor.author.fl_str_mv Soardi, Fernanda Caroline, 1980-
Mello, Maricilda Palandi de, 1954-
dc.subject.por.fl_str_mv Hiperplasia suprarrenal congênita
Genética molecular
Adrenal hyperplasia, Congenital
Molecular genetics.
Artigo original
topic Hiperplasia suprarrenal congênita
Genética molecular
Adrenal hyperplasia, Congenital
Molecular genetics.
Artigo original
description Agradecimentos: This study was supported by Karolinska Institutet, Stockholm County Council, The Marianne and Marcus Wallenberg Foundation, Stiftelsen Frimurare Barnhuset, Sallskapet Barnavard, the Soderberg Foundation, the Novo Nordisk Foundation and the Swedish Research Council (Project No. 12198 to A.W.). F.C.S. was supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasil (CAPES Grant No. 1919-5)
publishDate 2014
dc.date.none.fl_str_mv 2014
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.uri.fl_str_mv https://hdl.handle.net/20.500.12733/355
SOARDI, Fernanda Caroline; MELLO, Maricilda Palandi de. In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia. Clinical endocrinology. Chichester : Wiley, 2014. Vol. 82, n. 1 (Jan., 2014), p. 37-44. Disponível em: https://hdl.handle.net/20.500.12733/355. Acesso em: 24 mai. 2023.
url https://hdl.handle.net/20.500.12733/355
identifier_str_mv SOARDI, Fernanda Caroline; MELLO, Maricilda Palandi de. In vitro functional studies of rare CYP21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia. Clinical endocrinology. Chichester : Wiley, 2014. Vol. 82, n. 1 (Jan., 2014), p. 37-44. Disponível em: https://hdl.handle.net/20.500.12733/355. Acesso em: 24 mai. 2023.
dc.language.iso.fl_str_mv Inglês
language_invalid_str_mv Inglês
dc.relation.none.fl_str_mv https://repositorio.unicamp.br/acervo/detalhe/1231404
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório da Produção Científica e Intelectual da Unicamp
instname:Universidade Estadual de Campinas (UNICAMP)
instacron:UNICAMP
instname_str Universidade Estadual de Campinas (UNICAMP)
instacron_str UNICAMP
institution UNICAMP
reponame_str Repositório da Produção Científica e Intelectual da Unicamp
collection Repositório da Produção Científica e Intelectual da Unicamp
repository.name.fl_str_mv Repositório da Produção Científica e Intelectual da Unicamp - Universidade Estadual de Campinas (UNICAMP)
repository.mail.fl_str_mv reposip@unicamp.br
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