Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Arquivos Brasileiros de Endocrinologia & Metabologia (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302009000600013 |
Resumo: | OBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease. |
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Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenitaCongenital/hereditaryCongenital/neonatal diseasesCongenital/abnormalitiesadrenal insufficiencyframeshift mutationgenetic counselingOBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.Sociedade Brasileira de Endocrinologia e Metabologia2009-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302009000600013Arquivos Brasileiros de Endocrinologia & Metabologia v.53 n.6 2009reponame:Arquivos Brasileiros de Endocrinologia & Metabologia (Online)instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)instacron:SBEM10.1590/S0004-27302009000600013info:eu-repo/semantics/openAccessMantovani,Rafael MachadoPezzuti,Isabela LeiteDias,Vera Maria AlvesSilva,Ivani Novatoeng2009-10-28T00:00:00Zoai:scielo:S0004-27302009000600013Revistahttps://www.aem-sbem.com/ONGhttps://old.scielo.br/oai/scielo-oai.php||abem-editoria@endocrino.org.br1677-94870004-2730opendoar:2009-10-28T00:00Arquivos Brasileiros de Endocrinologia & Metabologia (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)false |
dc.title.none.fl_str_mv |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
title |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
spellingShingle |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita Mantovani,Rafael Machado Congenital/hereditary Congenital/neonatal diseases Congenital/abnormalities adrenal insufficiency frameshift mutation genetic counseling |
title_short |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
title_full |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
title_fullStr |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
title_full_unstemmed |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
title_sort |
Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita |
author |
Mantovani,Rafael Machado |
author_facet |
Mantovani,Rafael Machado Pezzuti,Isabela Leite Dias,Vera Maria Alves Silva,Ivani Novato |
author_role |
author |
author2 |
Pezzuti,Isabela Leite Dias,Vera Maria Alves Silva,Ivani Novato |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Mantovani,Rafael Machado Pezzuti,Isabela Leite Dias,Vera Maria Alves Silva,Ivani Novato |
dc.subject.por.fl_str_mv |
Congenital/hereditary Congenital/neonatal diseases Congenital/abnormalities adrenal insufficiency frameshift mutation genetic counseling |
topic |
Congenital/hereditary Congenital/neonatal diseases Congenital/abnormalities adrenal insufficiency frameshift mutation genetic counseling |
description |
OBJECTIVE: To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. CASE REPORT: We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. RESULTS: DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. CONCLUSION: A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-08-01 |
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 |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302009000600013 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27302009000600013 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0004-27302009000600013 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
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 |
Arquivos Brasileiros de Endocrinologia & Metabologia v.53 n.6 2009 reponame:Arquivos Brasileiros de Endocrinologia & Metabologia (Online) instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) instacron:SBEM |
instname_str |
Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
instacron_str |
SBEM |
institution |
SBEM |
reponame_str |
Arquivos Brasileiros de Endocrinologia & Metabologia (Online) |
collection |
Arquivos Brasileiros de Endocrinologia & Metabologia (Online) |
repository.name.fl_str_mv |
Arquivos Brasileiros de Endocrinologia & Metabologia (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
repository.mail.fl_str_mv |
||abem-editoria@endocrino.org.br |
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1754734810576715776 |