Navegando por Palavras-chave "Noonan syndrome"

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    Are Noonan syndrome and Noonan-like/multiple giant cell lesion syndrome distinct entities?
    (Wiley-Blackwell, 2001-01-22) Bertola, D. R.; Kim, C. A.; Pereira, A. C.; Mota, GFA; Krieger, J. E.; Vieira, I. C.; Valente, M.; Loreto, M. R.; Magalhaes, R. P.; Gonzalez, C. H.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    We report on a family with typical clinical findings of Noonan syndrome associated with giant cell lesions in maxilla and mandible. We discuss the obvious clinical overlap between Noonan syndrome and Noonan-like/multiple giant cell lesion syndrome, and we give further clinical and molecular support that these two entities could be allelic conditions. (C) 2001 Wiley-Liss, Inc.
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    CFC index for the diagnosis of cardiofaciocutaneous syndrome
    (Wiley-Blackwell, 2002-09-15) Kavamura, Maria Ines [UNIFESP]; Peres, Clovis de Araujo [UNIFESP]; Alchorne, Maurício Mota de Avelar [UNIFESP]; Brunoni, Decio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Controversy exists concerning the delineation of cardiofaciocutaneous syndrome (CFC). Many authors have attempted to establish syndrome traits for CFC, but to date none are pathognomonic or obligatory. We have created a clinical and objective method, called the CFC index, for CFC diagnosis. This method also differentiates CFC from Noonan syndrome and Costello syndrome, CFC's main differential diagnosis. We propose the use of the CFC index for the confirmation of CFC diagnosis and to differentiate CFC from other phenotypically similar genetic conditions, while molecular studies are still in progress. (C) 2002 Wiley-Liss, Inc.
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    Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: Overlapping clinical manifestations with Costello syndrome
    (Wiley-Blackwell, 2007-04-15) Narumi, Yoko; Aoki, Yoko; Niihori, Tetsuya; Neri, Giovanni; Cave, Helene; Verloes, Alain; Nava, Caroline; Kavamura, Maria Ines; Okamoto, Nobuhiko; Kurosawa, Kenji; Hennekam, Raoul C. M.; Wilson, Louise C.; Gillessen-Kaesbach, Gabriele; Wieczorek, Dagmar; Lapunzina, Pablo; Ohashi, Hirofumi; Makita, Yoshio; Kondo, Ikuko; Tsuchiya, Shigeru; Ito, Etsuro; Sameshima, Kiyoko; Kato, Kumi; Kure, Shigeo; Matsubara, Yokhi; Tohoku Univ; Univ Cattolica Sacro Cuore; Hop Robert Debre; Universidade Federal de São Paulo (UNIFESP); Osaka Med Ctr; Res Inst Maternal & Child Hlth; Kanagawa Childrens Med Ctr; Inst Child Hlth; Univ Amsterdam; Great Ormond St Hosp Sick Children; Univ Essen Gesamthsch; Univ Klinikum Schleswig Holstein; Hosp Univ La Paz; Saitama Childrens Med Ctr; Asahikawa Med Coll; Ibaraki Prefectural Handicapped Childrens Ctr; Hirosaki Univ
    Cardio-facio-cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by heart defects, a distinctive facial appearance, ectodermal abnormalities and mental retardation. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in two genes, PTPN11 and HRAS, respectively. Recently, we identified mutations in KRAS and BRAF in 19 of 43 individuals with CFC syndrome, suggesting that dysregulation of the RAS/RAF/MEK/ERK pathway is a molecular basis for CFC syndrome. the purpose of this study was to perform comprehensive mutation analysis in 56 patients with CFC syndrome and to investigate genotype-phenotype cot-relation. We analyzed KRAS, BRAF, and MAP2K1/2 (MEK1/2) in 13 new CFC patients and identified five BRAF and one MAP2K1 mutations in nine patients. We detected one MAP2K1 mutation in three patients and four new MAP2K2 mutations in four patients out of 24 patients without KRAS or BRAF mutations in the previous study [Niihori et al., 2006]. No mutations were identified in MAPK3/1(ERKI/2) in 21 patients without any mutations. in total, 35 of 56 (62.5%) patients with CFC syndrome had mutations (3 in KRAS, 24 in BRAF, and 8 in MAP2K1/2). No significant differences in clinical manifestations were found among 3 KRAS-positive patients, 16 BRAF-positive patients, and 6 MAP2K1/2-positive patients. Wrinkled palms and soles, hyperpigmentation and joint hyperextension, which have been commonly reported in Costello syndrome but not in CFC syndrome, were observed in 30-40% of the mutation-positive CFC patients, suggesting a significant clinical overlap between these two syndromes. (c) 2007 Wiley-Liss, Inc.
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    Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome
    (Nature Publishing Group, 2009-04-01) 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; 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
    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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    SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype-Phenotype Correlations
    (Wiley-Blackwell, 2011-07-01) Lepri, Francesca; De Luca, Alessandro; Stella, Lorenzo; Rossi, Cesare; Baldassarre, Giuseppina; Pantaleoni, Francesca; Cordeddu, Viviana; Williams, Bradley J.; Dentici, Maria L.; Caputo, Viviana; Venanzi, Serenella; Bonaguro, Michela; Kavamura, Ines [UNIFESP]; Faienza, Maria F.; Pilotta, Alba; Stanzial, Franco; Faravelli, Francesca; Gabrielli, Orazio; Marino, Bruno; Neri, Giovanni; Silengo, Margherita Cirillo; Ferrero, Giovanni B.; Torrrente, Isabella; Selicorni, Angelo; Mazzanti, Laura; Digilio, Maria C.; Zampino, Giuseppe; Dallapiccola, Bruno; Gelb, Bruce D.; Tartaglia, Marco; Ist Super Sanita; IRCCS Casa Sollievo Sofferenza; Univ Roma Tor Vergata; St Orsola Marcello Malpighi Hosp; Univ Turin; GeneDx; Universidade Federal de São Paulo (UNIFESP); Univ Bari; Osped Pediat; Osped Bolzano; Ospedali Galliera; Univ Politecn Marche; Univ Roma La Sapienza; Univ Cattolica Sacro Cuore; Univ Milano Bicocca; Univ Bologna; IRCCS; Mt Sinai Sch Med
    Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS is caused by aberrant RAS-MAPK signaling and is genetically heterogeneous, which explains, in part, the marked clinical variability documented for this Mendelian trait. Recently, we and others identified SOS1 as a major gene underlying NS. Here, we explored further the spectrum of SOS1 mutations and their associated phenotypic features. Mutation scanning of the entire SOS1 coding sequence allowed the identification of 33 different variants deemed to be of pathological significance, including 16 novel missense changes and in-frame indels. Various mutation clusters destabilizing or altering orientation of regions of the protein predicted to contribute structurally to the maintenance of autoinhibition were identified. Two previously unappreciated clusters predicted to enhance SOS1's recruitment to the plasma membrane, thus promoting a spatial reorientation of domains contributing to inhibition, were also recognized. Genotype-phenotype analysis confirmed our previous observations, establishing a high frequency of ectodermal anomalies and a low prevalence of cognitive impairment and reduced growth. Finally, mutation analysis performed on cohorts of individuals with nonsyndromic pulmonic stenosis, atrial septal defects, and ventricular septal defects excluded a major contribution of germline SOS1 lesions to the isolated occurrence of these cardiac anomalies. Hum Mutat 32:760-772, 2011. (C) 2011 Wiley-Liss, Inc.