Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay
Autor(a) principal: | |
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Data de Publicação: | 2003 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/27083 http://dx.doi.org/10.1210/jc.2001-011872 |
Resumo: | Combined pituitary hormone deficiency (CPHD) is characterized by impaired production of GH and one or more of the other anterior pituitary hormones. Prophet of Pit-1 (PROP-1), one of the pituitary specific homeodomain transcription factors, is involved in the differentiation of the anterior pituitary cells (somatotrophs, lactotrophs, thyrotrophs, and gonadotrophs), and PROP-1 gene mutations may interfere with the development of these cells, resulting in CPHD.We performed molecular analyses of the PROP-1 gene in two siblings, born to consanguineous parents, who presented with short stature. the index patient, a boy, was initially diagnosed with constitutional growth delay based on familial short stature, low parental target height, normal GH secretion, and imaging of the pituitary gland. On follow-up, auxological data and pubertal delay prompted a thorough reevaluation, which documented GH, TSH, and gonadotropin deficiencies. Direct sequencing of the PROP-1 gene revealed a novel homozygous transition 296G-->A in exon 2 in the two affected siblings. the mutation substitutes a highly conserved arginine by a glutamine at codon 99 (R99Q) in the second helix of the DNA-binding domain of the PROP-1 protein. Compared with wild-type PROP-1, R99Q displays a significant decrease in DNA binding on a paired box response element (PRDQ9) and trans-activation of a luciferase reporter gene.The findings emphasize the importance of repeated evaluations and illustrate that patients with CPHD associated with PROP-1 mutations present with a phenotypic spectrum, suggesting that the consequences of distinct PROP-1 mutations may be diverse and/or that additional factors, such as modifier genes, may have an impact on their expressivity. |
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Vieira, Teresa C. [UNIFESP]Dias-da-Silva, Magnus Régios [UNIFESP]Cerutti, Janete Maria [UNIFESP]Brunner, Elisa [UNIFESP]Borges, M. [UNIFESP]Arnaldi, Liliane Aparecida Teixeira [UNIFESP]Kopp, P.Abucham, Julio [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Northwestern Univ2016-01-24T12:33:38Z2016-01-24T12:33:38Z2003-01-01Journal of Clinical Endocrinology & Metabolism. Chevy Chase: Endocrine Soc, v. 88, n. 1, p. 38-44, 2003.0021-972Xhttp://repositorio.unifesp.br/handle/11600/27083http://dx.doi.org/10.1210/jc.2001-01187210.1210/jc.2001-011872WOS:000180459700008Combined pituitary hormone deficiency (CPHD) is characterized by impaired production of GH and one or more of the other anterior pituitary hormones. Prophet of Pit-1 (PROP-1), one of the pituitary specific homeodomain transcription factors, is involved in the differentiation of the anterior pituitary cells (somatotrophs, lactotrophs, thyrotrophs, and gonadotrophs), and PROP-1 gene mutations may interfere with the development of these cells, resulting in CPHD.We performed molecular analyses of the PROP-1 gene in two siblings, born to consanguineous parents, who presented with short stature. the index patient, a boy, was initially diagnosed with constitutional growth delay based on familial short stature, low parental target height, normal GH secretion, and imaging of the pituitary gland. On follow-up, auxological data and pubertal delay prompted a thorough reevaluation, which documented GH, TSH, and gonadotropin deficiencies. Direct sequencing of the PROP-1 gene revealed a novel homozygous transition 296G-->A in exon 2 in the two affected siblings. the mutation substitutes a highly conserved arginine by a glutamine at codon 99 (R99Q) in the second helix of the DNA-binding domain of the PROP-1 protein. Compared with wild-type PROP-1, R99Q displays a significant decrease in DNA binding on a paired box response element (PRDQ9) and trans-activation of a luciferase reporter gene.The findings emphasize the importance of repeated evaluations and illustrate that patients with CPHD associated with PROP-1 mutations present with a phenotypic spectrum, suggesting that the consequences of distinct PROP-1 mutations may be diverse and/or that additional factors, such as modifier genes, may have an impact on their expressivity.Universidade Federal de São Paulo, Escola Paulista Med, Dept Med, Div Endocrinol, BR-04039002 São Paulo, SP, BrazilNorthwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USAUniversidade Federal de São Paulo, Escola Paulista Med, Dept Med, Div Endocrinol, BR-04039002 São Paulo, SP, BrazilWeb of Science38-44engEndocrine SocJournal of Clinical Endocrinology & MetabolismFamilial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delayinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/270832022-07-08 10:45:11.736metadata only accessoai:repositorio.unifesp.br:11600/27083Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T13:45:11Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
title |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
spellingShingle |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay Vieira, Teresa C. [UNIFESP] |
title_short |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
title_full |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
title_fullStr |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
title_full_unstemmed |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
title_sort |
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of prophet of Pit-1 presenting as constitutional growth delay |
author |
Vieira, Teresa C. [UNIFESP] |
author_facet |
Vieira, Teresa C. [UNIFESP] Dias-da-Silva, Magnus Régios [UNIFESP] Cerutti, Janete Maria [UNIFESP] Brunner, Elisa [UNIFESP] Borges, M. [UNIFESP] Arnaldi, Liliane Aparecida Teixeira [UNIFESP] Kopp, P. Abucham, Julio [UNIFESP] |
author_role |
author |
author2 |
Dias-da-Silva, Magnus Régios [UNIFESP] Cerutti, Janete Maria [UNIFESP] Brunner, Elisa [UNIFESP] Borges, M. [UNIFESP] Arnaldi, Liliane Aparecida Teixeira [UNIFESP] Kopp, P. Abucham, Julio [UNIFESP] |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Northwestern Univ |
dc.contributor.author.fl_str_mv |
Vieira, Teresa C. [UNIFESP] Dias-da-Silva, Magnus Régios [UNIFESP] Cerutti, Janete Maria [UNIFESP] Brunner, Elisa [UNIFESP] Borges, M. [UNIFESP] Arnaldi, Liliane Aparecida Teixeira [UNIFESP] Kopp, P. Abucham, Julio [UNIFESP] |
description |
Combined pituitary hormone deficiency (CPHD) is characterized by impaired production of GH and one or more of the other anterior pituitary hormones. Prophet of Pit-1 (PROP-1), one of the pituitary specific homeodomain transcription factors, is involved in the differentiation of the anterior pituitary cells (somatotrophs, lactotrophs, thyrotrophs, and gonadotrophs), and PROP-1 gene mutations may interfere with the development of these cells, resulting in CPHD.We performed molecular analyses of the PROP-1 gene in two siblings, born to consanguineous parents, who presented with short stature. the index patient, a boy, was initially diagnosed with constitutional growth delay based on familial short stature, low parental target height, normal GH secretion, and imaging of the pituitary gland. On follow-up, auxological data and pubertal delay prompted a thorough reevaluation, which documented GH, TSH, and gonadotropin deficiencies. Direct sequencing of the PROP-1 gene revealed a novel homozygous transition 296G-->A in exon 2 in the two affected siblings. the mutation substitutes a highly conserved arginine by a glutamine at codon 99 (R99Q) in the second helix of the DNA-binding domain of the PROP-1 protein. Compared with wild-type PROP-1, R99Q displays a significant decrease in DNA binding on a paired box response element (PRDQ9) and trans-activation of a luciferase reporter gene.The findings emphasize the importance of repeated evaluations and illustrate that patients with CPHD associated with PROP-1 mutations present with a phenotypic spectrum, suggesting that the consequences of distinct PROP-1 mutations may be diverse and/or that additional factors, such as modifier genes, may have an impact on their expressivity. |
publishDate |
2003 |
dc.date.issued.fl_str_mv |
2003-01-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T12:33:38Z |
dc.date.available.fl_str_mv |
2016-01-24T12:33:38Z |
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.citation.fl_str_mv |
Journal of Clinical Endocrinology & Metabolism. Chevy Chase: Endocrine Soc, v. 88, n. 1, p. 38-44, 2003. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/27083 http://dx.doi.org/10.1210/jc.2001-011872 |
dc.identifier.issn.none.fl_str_mv |
0021-972X |
dc.identifier.doi.none.fl_str_mv |
10.1210/jc.2001-011872 |
dc.identifier.wos.none.fl_str_mv |
WOS:000180459700008 |
identifier_str_mv |
Journal of Clinical Endocrinology & Metabolism. Chevy Chase: Endocrine Soc, v. 88, n. 1, p. 38-44, 2003. 0021-972X 10.1210/jc.2001-011872 WOS:000180459700008 |
url |
http://repositorio.unifesp.br/handle/11600/27083 http://dx.doi.org/10.1210/jc.2001-011872 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Clinical Endocrinology & Metabolism |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
38-44 |
dc.publisher.none.fl_str_mv |
Endocrine Soc |
publisher.none.fl_str_mv |
Endocrine Soc |
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 |
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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 |
|
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1802764151375790080 |