Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31394 http://dx.doi.org/10.1038/ejhg.2008.188 |
Resumo: | Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. the NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. in a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype-phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects. |
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Neumann, Thomas E.Allanson, JudithKavamura, Ines [UNIFESP]Kerr, BronwynNeri, GiovanniNoonan, JacquelineCordeddu, VivianaGibson, KateTzschach, AndreasKrueger, GabrieleHoeltzenbein, MariaGoecke, Timm O.Kehl, Hans GerdAlbrecht, BeateLuczak, KlaudiuszSasiadek, Maria M.Musante, LucianaLaurie, RohanPeters, HartmutTartaglia, MarcoZenker, MartinKalscheuer, VeraUniv Erlangen NurnbergUniv Hosp MunsterChildrens Hosp Eastern OntarioUniversidade Federal de São Paulo (UNIFESP)Royal Manchester Childrens HospUniv CattolicaUniv KentuckyIst Super SanitaRoyal Childrens HospMax Planck Inst Mol GenetUniv Hosp RostockUniv Hosp DusseldorfUniv Hosp EssenWroclaw Med UnivMater Pathol ServUniv Hosp Charite2016-01-24T13:52:22Z2016-01-24T13:52:22Z2009-04-01European Journal of Human Genetics. London: Nature Publishing Group, v. 17, n. 4, p. 420-425, 2009.1018-4813http://repositorio.unifesp.br/handle/11600/31394http://dx.doi.org/10.1038/ejhg.2008.18810.1038/ejhg.2008.188WOS:000264354900004Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. the NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. in a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype-phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects.German Research Foundation (DFG)Telethon-ItalyAssociazione ONLUSUniv Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-8520 Erlangen, GermanyUniv Hosp Munster, Dept Human Genet, Munster, GermanyChildrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, CanadaUniversidade Federal de São Paulo, São Paulo, BrazilRoyal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, EnglandUniv Cattolica, Inst Med Genet, Rome, ItalyUniv Kentucky, Coll Med, Div Cardiol, Dept Pediat, Lexington, KY USAIst Super Sanita, Dipartimento Biol Cellulare & Neurosci, I-00161 Rome, ItalyRoyal Childrens Hosp, Genet Hlth Queensland, Herston, Qld, AustraliaMax Planck Inst Mol Genet, Berlin, GermanyUniv Hosp Rostock, Med Genet Unit, Dept Pediat, Rostock, GermanyUniv Hosp Dusseldorf, Dept Human Genet, Dusseldorf, GermanyUniv Hosp Munster, Dept Pediat Cardiol, Munster, GermanyUniv Hosp Essen, Dept Human Genet, Essen, GermanyWroclaw Med Univ, Dept Maxilla Facial Surg, Wroclaw, PolandWroclaw Med Univ, Dept Genet, Wroclaw, PolandMater Pathol Serv, Brisbane, Qld, AustraliaUniv Hosp Charite, Dept Med Genet, Berlin, GermanyUniversidade Federal de São Paulo, São Paulo, BrazilGerman Research Foundation (DFG): Ze 524/4-1Telethon-Italy: GGP07115Web of Science420-425engNature Publishing GroupEuropean Journal of Human GeneticsNoonan syndromecardio-facio-cutaneous syndromemultiple giant cell lesionsNoonan-like/multiple giant cell lesion syndromeRAS-MAPK signaling cascadeMultiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndromeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/313942016-01-24 11:52:22.639metadata only accessoai:repositorio.unifesp.br:11600/31394Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652016-01-24T13:52:22Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
title |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
spellingShingle |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome Neumann, Thomas E. Noonan syndrome cardio-facio-cutaneous syndrome multiple giant cell lesions Noonan-like/multiple giant cell lesion syndrome RAS-MAPK signaling cascade |
title_short |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
title_full |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
title_fullStr |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
title_full_unstemmed |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
title_sort |
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome |
author |
Neumann, Thomas E. |
author_facet |
Neumann, Thomas E. Allanson, Judith Kavamura, Ines [UNIFESP] Kerr, Bronwyn Neri, Giovanni Noonan, Jacqueline Cordeddu, Viviana Gibson, Kate Tzschach, Andreas Krueger, Gabriele Hoeltzenbein, Maria Goecke, Timm O. Kehl, Hans Gerd Albrecht, Beate Luczak, Klaudiusz Sasiadek, Maria M. Musante, Luciana Laurie, Rohan Peters, Hartmut Tartaglia, Marco Zenker, Martin Kalscheuer, Vera |
author_role |
author |
author2 |
Allanson, Judith Kavamura, Ines [UNIFESP] Kerr, Bronwyn Neri, Giovanni Noonan, Jacqueline Cordeddu, Viviana Gibson, Kate Tzschach, Andreas Krueger, Gabriele Hoeltzenbein, Maria Goecke, Timm O. Kehl, Hans Gerd Albrecht, Beate Luczak, Klaudiusz Sasiadek, Maria M. Musante, Luciana Laurie, Rohan Peters, Hartmut Tartaglia, Marco Zenker, Martin Kalscheuer, Vera |
author2_role |
author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Univ Erlangen Nurnberg Univ Hosp Munster Childrens Hosp Eastern Ontario Universidade Federal de São Paulo (UNIFESP) Royal Manchester Childrens Hosp Univ Cattolica Univ Kentucky Ist Super Sanita Royal Childrens Hosp Max Planck Inst Mol Genet Univ Hosp Rostock Univ Hosp Dusseldorf Univ Hosp Essen Wroclaw Med Univ Mater Pathol Serv Univ Hosp Charite |
dc.contributor.author.fl_str_mv |
Neumann, Thomas E. Allanson, Judith Kavamura, Ines [UNIFESP] Kerr, Bronwyn Neri, Giovanni Noonan, Jacqueline Cordeddu, Viviana Gibson, Kate Tzschach, Andreas Krueger, Gabriele Hoeltzenbein, Maria Goecke, Timm O. Kehl, Hans Gerd Albrecht, Beate Luczak, Klaudiusz Sasiadek, Maria M. Musante, Luciana Laurie, Rohan Peters, Hartmut Tartaglia, Marco Zenker, Martin Kalscheuer, Vera |
dc.subject.eng.fl_str_mv |
Noonan syndrome cardio-facio-cutaneous syndrome multiple giant cell lesions Noonan-like/multiple giant cell lesion syndrome RAS-MAPK signaling cascade |
topic |
Noonan syndrome cardio-facio-cutaneous syndrome multiple giant cell lesions Noonan-like/multiple giant cell lesion syndrome RAS-MAPK signaling cascade |
description |
Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. the NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only genetic abnormalities reported so far in some patients with NL/MGCLS and in one individual with LEOPARD syndrome and MGCL. in a cohort of 75 NS patients previously tested negative for mutations in PTPN11 and KRAS, we detected SOS1 mutations in 11 individuals, four of whom had MGCL. To explore further the relevance of aberrant RAS-MAPK signaling in syndromic MGCL, we analyzed the established genes causing CFCS in three subjects with MGCL associated with a phenotype fitting CFCS. Mutations in BRAF or MEK1 were identified in these patients. All mutations detected in these seven patients with syndromic MGCL had previously been described in NS or CFCS without apparent MGCL. This study demonstrates that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype-phenotype correlation. This suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS and CFCS rather than specific mutation effects. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-04-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:52:22Z |
dc.date.available.fl_str_mv |
2016-01-24T13:52:22Z |
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 |
European Journal of Human Genetics. London: Nature Publishing Group, v. 17, n. 4, p. 420-425, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31394 http://dx.doi.org/10.1038/ejhg.2008.188 |
dc.identifier.issn.none.fl_str_mv |
1018-4813 |
dc.identifier.doi.none.fl_str_mv |
10.1038/ejhg.2008.188 |
dc.identifier.wos.none.fl_str_mv |
WOS:000264354900004 |
identifier_str_mv |
European Journal of Human Genetics. London: Nature Publishing Group, v. 17, n. 4, p. 420-425, 2009. 1018-4813 10.1038/ejhg.2008.188 WOS:000264354900004 |
url |
http://repositorio.unifesp.br/handle/11600/31394 http://dx.doi.org/10.1038/ejhg.2008.188 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
European Journal of Human Genetics |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
420-425 |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
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 |
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1802764119512711168 |