Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients
- Autores
- Minutolo, Carolina; Nadra, Alejandro D.; Fernández, Cecilia; Taboas, Melisa; Buzzalino, Noemí; Casali, Bárbara; Belli, Susana; Charreau, Eduardo H.; Alba, Liliana; Dain, Liliana
- Año de publicación
- 2011
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fil: Minutolo, Carolina. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Fil: Nadra, Alejandro D. Universidad de Buenos Aires. Departamento de Fisiología Biología Molecular y Celular; Argentina.
Fil: Fernández, Cecilia. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Fil: Taboas, Melisa. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Fil: Buzzalino, Noemí. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Fil: Casali, Bárbara. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Fil: Belli, Susana. Hospital Durand. División Endocrinología; Argentina.
Fil: Charreau, Eduardo H. Instituto de Biología y Medicina Experimental; Argentina.
Fil: Alba, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Fil: Dain, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients. - Fuente
- PloS One 2011; 6(1): e15899.
- Materia
-
Mutación
Esteroide 21-Hidroxilasa - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- Repositorio
- Institución
- Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
- OAI Identificador
- oai:sgc.anlis.gob.ar:123456789/397
Ver los metadatos del registro completo
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Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patientsMinutolo, CarolinaNadra, Alejandro D.Fernández, CeciliaTaboas, MelisaBuzzalino, NoemíCasali, BárbaraBelli, SusanaCharreau, Eduardo H.Alba, LilianaDain, LilianaMutaciónEsteroide 21-HidroxilasaFil: Minutolo, Carolina. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Nadra, Alejandro D. Universidad de Buenos Aires. Departamento de Fisiología Biología Molecular y Celular; Argentina.Fil: Fernández, Cecilia. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Taboas, Melisa. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Buzzalino, Noemí. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Casali, Bárbara. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Belli, Susana. Hospital Durand. División Endocrinología; Argentina.Fil: Charreau, Eduardo H. Instituto de Biología y Medicina Experimental; Argentina.Fil: Alba, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Fil: Dain, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina.Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients.Yes2011info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdf1932-6203http://sgc.anlis.gob.ar/handle/123456789/397http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019215/pdf/pone.0015899.pdf10.1371/journal.pone.0015899.PloS One 2011; 6(1): e15899.reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLISPlos oneenginfo:eu-repo/semantics/openAccess2025-09-29T14:29:59Zoai:sgc.anlis.gob.ar:123456789/397Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-09-29 14:30:00.539Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false |
dc.title.none.fl_str_mv |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
title |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
spellingShingle |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients Minutolo, Carolina Mutación Esteroide 21-Hidroxilasa |
title_short |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
title_full |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
title_fullStr |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
title_full_unstemmed |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
title_sort |
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients |
dc.creator.none.fl_str_mv |
Minutolo, Carolina Nadra, Alejandro D. Fernández, Cecilia Taboas, Melisa Buzzalino, Noemí Casali, Bárbara Belli, Susana Charreau, Eduardo H. Alba, Liliana Dain, Liliana |
author |
Minutolo, Carolina |
author_facet |
Minutolo, Carolina Nadra, Alejandro D. Fernández, Cecilia Taboas, Melisa Buzzalino, Noemí Casali, Bárbara Belli, Susana Charreau, Eduardo H. Alba, Liliana Dain, Liliana |
author_role |
author |
author2 |
Nadra, Alejandro D. Fernández, Cecilia Taboas, Melisa Buzzalino, Noemí Casali, Bárbara Belli, Susana Charreau, Eduardo H. Alba, Liliana Dain, Liliana |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
Mutación Esteroide 21-Hidroxilasa |
topic |
Mutación Esteroide 21-Hidroxilasa |
dc.description.none.fl_txt_mv |
Fil: Minutolo, Carolina. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Fil: Nadra, Alejandro D. Universidad de Buenos Aires. Departamento de Fisiología Biología Molecular y Celular; Argentina. Fil: Fernández, Cecilia. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Fil: Taboas, Melisa. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Fil: Buzzalino, Noemí. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Fil: Casali, Bárbara. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Fil: Belli, Susana. Hospital Durand. División Endocrinología; Argentina. Fil: Charreau, Eduardo H. Instituto de Biología y Medicina Experimental; Argentina. Fil: Alba, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Fil: Dain, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients. |
description |
Fil: Minutolo, Carolina. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Argentina. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011 |
dc.type.none.fl_str_mv |
info:ar-repo/semantics/articulo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
1932-6203 http://sgc.anlis.gob.ar/handle/123456789/397 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019215/pdf/pone.0015899.pdf 10.1371/journal.pone.0015899. |
identifier_str_mv |
1932-6203 10.1371/journal.pone.0015899. |
url |
http://sgc.anlis.gob.ar/handle/123456789/397 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019215/pdf/pone.0015899.pdf |
dc.language.none.fl_str_mv |
eng |
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eng |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
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publisher.none.fl_str_mv |
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dc.source.none.fl_str_mv |
PloS One 2011; 6(1): e15899. reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán" instacron:ANLIS |
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Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán" |
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