Pauli, Silke

[["dc.bibliographiccitation.firstpage","1392"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","British Journal of Cancer"],["dc.bibliographiccitation.lastpage","1397"],["dc.bibliographiccitation.volume","112"],["dc.contributor.author","Kratz, Christian P."],["dc.contributor.author","Franke, L."],["dc.contributor.author","Peters, H."],["dc.contributor.author","Kohlschmidt, N."],["dc.contributor.author","Kazmierczak, B."],["dc.contributor.author","Finckh, U."],["dc.contributor.author","Bier, Andrea"],["dc.contributor.author","Eichhorn, B."],["dc.contributor.author","Blank, C."],["dc.contributor.author","Kraus, Cornelia"],["dc.contributor.author","Kohlhase, Juergen"],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Wildhardt, G."],["dc.contributor.author","Kutsche, Kerstin"],["dc.contributor.author","Auber, Bernd"],["dc.contributor.author","Christmann, A."],["dc.contributor.author","Bachmann, N."],["dc.contributor.author","Mitter, D."],["dc.contributor.author","Cremer, F. W."],["dc.contributor.author","Mayer, K."],["dc.contributor.author","Daumer-Haas, C."],["dc.contributor.author","Nevinny-Stickel-Hinzpeter, C."],["dc.contributor.author","Oeffner, Frank"],["dc.contributor.author","Schlueter, G."],["dc.contributor.author","Gencik, M."],["dc.contributor.author","Ueberlacker, B."],["dc.contributor.author","Lissewski, Christina"],["dc.contributor.author","Schanze, I."],["dc.contributor.author","Greene, M. H."],["dc.contributor.author","Spix, C."],["dc.contributor.author","Zenker, Martin"],["dc.date.accessioned","2018-11-07T09:58:32Z"],["dc.date.available","2018-11-07T09:58:32Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown. Methods: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry. Results: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR) = 10.5, 95% confidence interval = 5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia = 4; brain tumour = 3; acute lymphoblastic leukaemia = 2; rhabdomyosarcoma = 2; and neuroblastoma = 1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4. Conclusions: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours."],["dc.identifier.doi","10.1038/bjc.2015.75"],["dc.identifier.isi","000352989900012"],["dc.identifier.pmid","25742478"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37381"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1532-1827"],["dc.relation.issn","0007-0920"],["dc.title","Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","651"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","656"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Zenker, Martin"],["dc.contributor.author","Horn, Denise"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Allanson, Judith E."],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","van der Burgt, Ineke"],["dc.contributor.author","Doerr, Helmuth-Guenther"],["dc.contributor.author","Gaspar, Harald"],["dc.contributor.author","Hofbeck, Michael"],["dc.contributor.author","Gillessen-Kaesbach, Gabriele"],["dc.contributor.author","Koch, Andreas"],["dc.contributor.author","Meinecke, Peter"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Nowka, Anja"],["dc.contributor.author","Rauch, Anita"],["dc.contributor.author","Reif, Silke"],["dc.contributor.author","von Schnakenburg, Christian"],["dc.contributor.author","Seidel, Heide"],["dc.contributor.author","Wehner, Lars-Erik"],["dc.contributor.author","Zweier, Christiane"],["dc.contributor.author","Bauhuber, Susanne"],["dc.contributor.author","Matejas, Verena"],["dc.contributor.author","Kratz, Christian P."],["dc.contributor.author","Thomas, Christoph"],["dc.contributor.author","Kutsche, Kerstin"],["dc.date.accessioned","2018-11-07T10:58:11Z"],["dc.date.available","2018-11-07T10:58:11Z"],["dc.date.issued","2007"],["dc.description.abstract","Background: Heterozygous gain- of- function mutations in various genes encoding proteins of the Ras- MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome ( NS) and cardio- facio- cutaneous syndrome ( CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS. Methods and results: We investigated SOS1 in a large cohort of patients with disorders of the NS - CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene. Conclusion: We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gainoffunction mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically."],["dc.identifier.doi","10.1136/jmg.2007.051276"],["dc.identifier.isi","000249889300009"],["dc.identifier.pmid","17586837"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50423"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","B M J Publishing Group"],["dc.relation.issn","0022-2593"],["dc.title","SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","787"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","796"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Martinelli, Simone"],["dc.contributor.author","Stellacci, Emilia"],["dc.contributor.author","Pannone, Luca"],["dc.contributor.author","D'Agostino, Daniela"],["dc.contributor.author","Consoli, Federica"],["dc.contributor.author","Lissewski, Christina"],["dc.contributor.author","Silvano, Marianna"],["dc.contributor.author","Cencelli, Giulia"],["dc.contributor.author","Lepri, Francesca"],["dc.contributor.author","Maitz, Silvia"],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Rauch, Anita"],["dc.contributor.author","Zampino, Giuseppe"],["dc.contributor.author","Selicorni, Angelo"],["dc.contributor.author","Melancon, Serge"],["dc.contributor.author","Digilio, Maria C."],["dc.contributor.author","Gelb, Bruce D."],["dc.contributor.author","De Luca, Alessandro"],["dc.contributor.author","Dallapiccola, Bruno"],["dc.contributor.author","Zenker, Martin"],["dc.contributor.author","Tartaglia, Marco"],["dc.date.accessioned","2018-11-07T09:54:03Z"],["dc.date.available","2018-11-07T09:54:03Z"],["dc.date.issued","2015"],["dc.description.abstract","Noonan syndrome (NS) is a relatively common developmental disorder with a pleomorphic phenotype. Mutations causing NS alter genes encoding proteins involved in the RAS-MAPK pathway. We and others identified Casitas B-lineage lymphoma proto-oncogene (CBL), which encodes an E3-ubiquitin ligase acting as a tumor suppressor in myeloid malignancies, as a disease gene underlying a condition clinically related to NS. Here, we further explored the spectrum of germline CBL mutations and their associated phenotype. CBL mutation scanning performed on 349 affected subjects with features overlapping NS and no mutation in NS genes allowed the identification of five different variants with pathological significance. Among them, two splice-site changes, one in-frame deletion, and one missense mutation affected the RING domain and/or the adjacent linker region, overlapping cancer-associated defects. A novel nonsense mutation generating a v-Cbl-like protein able to enhance signal flow through RAS was also identified. Genotype-phenotype correlation analysis performed on available records indicated that germline CBL mutations cause a variable phenotype characterized by a relatively high frequency of neurological features, predisposition to juvenile myelomonocytic leukemia, and low prevalence of cardiac defects, reduced growth, and cryptorchidism. Finally, we excluded a major contribution of two additional members of the CBL family, CBLB and CBLC, to NS and related disorders."],["dc.identifier.doi","10.1002/humu.22809"],["dc.identifier.isi","000358376600008"],["dc.identifier.pmid","25952305"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36458"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.title","Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1960"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","1966"],["dc.bibliographiccitation.volume","152A"],["dc.contributor.author","Allanson, Judith E."],["dc.contributor.author","Bohring, Axel"],["dc.contributor.author","Dorr, Helmuth-Guenther"],["dc.contributor.author","Dufke, Andreas"],["dc.contributor.author","Gillessen-Kaesbach, Gabrielle"],["dc.contributor.author","Horn, Denise"],["dc.contributor.author","Koenig, Rainer"],["dc.contributor.author","Kratz, Christian P."],["dc.contributor.author","Kutsche, Kerstin"],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Raskin, Salmo"],["dc.contributor.author","Rauch, Anita"],["dc.contributor.author","Turner, Anne"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Zenker, Martin"],["dc.date.accessioned","2018-11-07T08:40:31Z"],["dc.date.available","2018-11-07T08:40:31Z"],["dc.date.issued","2010"],["dc.description.abstract","The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway. Thirty-two of this cohort have PTPN11 mutations, 21 SOS1 mutations, 11 RAF1 mutations, and 17 KRAS mutations. The facial appearance of each person was judged to be typical of Noonan syndrome or atypical. In each gene category both typical and unusual faces were found. We determined that some individuals with mutations in the most commonly affected gene, PTPN11, which is correlated with the cardinal physical features, may have a quite atypical face. Conversely, some individuals with KRAS mutations, which may be associated with a less characteristic intellectual phenotype and a resemblance to Costello and cardio-facio-cutaneous syndromes, can have a very typical face. Thus, the facial phenotype, alone, is insufficient to predict the genotype, but certain facial features may facilitate an educated guess in some cases. (C) 2010 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/ajmg.a.33518"],["dc.identifier.isi","000280925800010"],["dc.identifier.pmid","20602484"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19253"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1552-4825"],["dc.title","The Face of Noonan Syndrome: Does Phenotype Predict Genotype"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]