References
- Noonan JA. Hypertelorism with Turner phenotype: a new syndrome with associated congenital heart disease. Am J Dis Child. 1968;116:373–380.
- Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet. 2013;14:355–369.
- Roberts AE, Allanson JE, Tartaglia M, et al. Noonan syndrome. Lancet. 2013;381:333–342.
- van Der Burgt I, Brunner H. Genetic heterogeneity in Noonan syndrome: evidence for an autosomal recessive form. Am J Med Genet. 2000;94(1):46–51.
- Tafazoli A, Eshraghi P, Koleti ZK, et al. Noonan syndrome – a new survey. Arch Med Sci. 2017;13(1):215–222.
- Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7:295–308.
- Fernandez-Medarde A, Santos E. Ras in cancer and developmental diseases. Genes Cancer. 2011;2:344–358.
- Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3:459–465.
- Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3:11–22.
- Cawthon RM, O’Connell P, Buchberg AM, et al. Identification and characterization of transcripts from the neurofibromatosis 1 region: the sequence and genomic structure of EVI2 and mapping of other transcripts. Genomics. 1990;7:555–565.
- Tartaglia M, Mehler EL, Goldberg R, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001;29:465–468.
- Tartaglia M, Pennacchio LA, Zhao C, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2006;39:75–79.
- Carta C, Pantaleoni F, Bocchinfuso G, et al. Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet. 2006;79:129–135.
- Schubbert S, Zenker M, Rowe SL, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet. 2006;38:331–336.
- Pandit B, Sarkozy A, Pennacchio LA, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007;39:1007–1012.
- Aoki Y, Niihori T, Kawame H, et al. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet. 2005;37:1038–1040.
- Cirstea IC, Kutsche K, Dvorsky R, et al. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet. 2010;42:27–29.
- Denayer E, Peeters H, Sevenants L, et al. NRAS mutations in Noonan syndrome. Mol Syndromol. 2012;3:34–38.
- Gos M, Fahiminiya S, Poznański J, et al. Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity. Am J Med Genet A. 2014;164A:2310–2316.
- Martinelli S, De Luca A, Stellacci E, et al. Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype. Am J Hum Genet. 2010;87:250–257.
- Nava C, Hanna N, Michot C, et al. Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype–phenotype relationships and overlap with Costello syndrome. J Med Genet. 2007;44:763–771.
- Niihori T, Aoki Y, Narumi Y, et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006;38:294–296.
- Razzaque MA, Nishizawa T, Komoike Y, et al. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet. 2007;39:1013–1017.
- Sarkozy A, Carta C, Moretti S, et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009;30:695–702.
- Aoki Y, Niihori T, Banjo T, et al. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genet. 2013;93:173–180.
- Tidyman WE, Rauen KA. Expansion of the RASopathies. Curr Genet Med Rep. 2016;4(3):57–64.
- Vissers LE, Bonetti M, Paardekooper Overman J, et al. Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. Eur J Hum Genet. 2015;23:317–324.
- Yamamoto GL, Aguena M, Gos M, et al. Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. J Med Genet. 2015;52:413–421.
- Higgins EM, Bos JM, Mason-Suares H, et al. Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy. JCI Insight. 2017;2(5):e91225.
- Aoki Y, Niihori T, Inoue SI, et al. Recent advances in RASopathies. J Hum Genet. 2016;61(1):33–39.
- Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011;25:161–179.
- Flex E, Jaiswal M, Pantaleoni F, et al. Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis. Hum Mol Genet. 2014;23:4315–4327.
- Chen PC, Yin J, Yu HW, et al. Next-generation sequencing identifies rare variants associated with Noonan syndrome. Proc Natl Acad Sci USA. 2014;111:11473–11478.
- Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010;126:746–759.
- Shchelochkov OA, Patel A, Weissenberger GM, et al. Duplication of chromosome band 12q24. 11q24. 23 results in apparent Noonan syndrome. Am J Med Genet A. 2008;146:1042–1048.
- Tartaglia M, Kalidas K, Shaw A, et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002;70:1555–1563.
- Tartaglia M, Gelb BD. Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms. Ann NY Acad Sci. 2010;1214:99–121.
- Zenker M, Horn D, Wieczorek D, et al. SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. J Med Genet. 2007;44:651–656.
- Lee BH, Kim JM, Jin HY, et al. Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. J Pediatr. 2011;159:1029–1035.
- Bertola DR, Pereira AC, de Oliveira PS, et al. Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. Am J Med Genet A. 2004;130A:378–383.
- Bentires-Alj M, Kontaridis MI, Neel BG. Stops along the RAS pathway in human genetic disease. Nat Med. 2006;12:283–285.
- Zenker M, Voss E, Reis A. Mild variable Noonan syndrome in a family with a novel PTPN11 mutation. Eur J Med Genet. 2007;50:43–47.
- Hernández-Porras I, Guerra C. Modeling RASopathies with genetically modified mouse models. Methods Mol Biol. 2017;1487:379–408.
- Jindal GA, Goyal Y, Burdine RD, et al. RASopathies: unraveling mechanisms with animal models. Dis Model Mech. 2015;8:1167.
- Araki T, Mohi MG, Ismat FA, et al. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med. 2004;10:849–857.
- Araki T, Chan G, Newbigging S, et al. Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation. Proc Natl Acad Sci USA. 2009;106:4736–4741.
- Yi JS, Huang Y, Kwaczala AT, et al. Low-dose dasatinib rescues cardiac function in Noonan syndrome. JCI Insight. 2016;1(20):e90220.
- Altmüller F, Pothula S, Annamneedi A, et al. Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy. PLoS Genet. 2017;13(3):e1006684.
- Pages G, Guerin S, Grall D, et al. Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science. 1999;286:1374–1377.
- Nakamura T, Gulick J, Pratt R, et al. Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations. Proc Natl Acad Sci USA. 2009;106:15436–15441.
- Krenz M, Gulick J, Osinska HE, et al. Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci USA. 2008;105:18930–18935.
- Chan G, Kalaitzidis D, Usenko T, et al. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis. Blood. 2009;113:4414–4424.
- Nakamura T, Colbert M, Krenz M, et al. Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. J Clin Invest. 2007;117:2123–2132.
- Wu X, Simpson J, Hong JH, et al. MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1(L613V) mutation. J Clin Invest. 2011;121:1009–1025.
- Yin JC, Platt MJ, Tian X, et al. Cellular interplay via cytokine hierarchy causes pathological cardiac hypertrophy in RAF1-mutant Noonan syndrome. Nat Commun. 2017;8:15518.
- Hernandez-Porras I, Fabbiano S, Schuhmacher AJ, et al. K-RasV14I recapitulates Noonan syndrome in mice. Proc Natl Acad Sci USA. 2014;111:16395–16400.
- Hernandez-Porras I, Jimenez-Catalan B, Schuhmacher AJ, et al. The impact of genetic backgrounds in the K-RasV14I-induced Noonan syndrome. Rare Diseases. 2015;3:e1045169.
- Forbes SA, Beare D, Boutselakis H, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 2017;45(D1):D777-D783. Available from: http://cancer.sanger.ac.uk/cosmic
- Chan IT, Kutok JL, Williams IR, et al. Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J Clin Invest. 2004;113(4):528–538.
- Barford D, Neel BG. Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure. 1998;6:249–254.
- Hof P, Pluskey S, Dhe-Paganon S, et al. Crystal structure of the tyrosine phosphatase SHP-2. Cell. 1998;92:441–450.
- Perrinjaquet M, Vilar M, Ibanez CF. Protein-tyrosine phosphatase SHP2 contributes to GDNF neurotrophic activity through direct binding to phospho-Tyr687 in the RET receptor tyrosine kinase. J Biol Chem. 2010;285:31867–31875.
- Li H, Tao C, Cai Z, et al. Frs2alpha and Shp2 signal independently of Gab to mediate FGF signaling in lens development. J Cell Sci. 2014;127:571–582.
- Bode JG, Schweigart J, Kehrmann J, et al. TNF-alpha induces tyrosine phosphorylation and recruitment of the Src homology protein-tyrosine phosphatase 2 to the gp130 signal-transducing subunit of the IL-6 receptor complex. J Immunol. 2003;171:257–266.
- Tajan M, de Rocca Serra A, Valet P, et al. SHP2 sails from physiology to pathology. Eur J Med Genet. 2015;58:509–525.
- Grossmann KS, Rosario M, Birchmeier C, et al. The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res. 2010;106:53–89.
- Zhang SQ, Tsiaras WG, Araki T, et al. Receptor-specific regulation of phosphatidylinositol 3ʹ-kinase activation by the protein tyrosine phosphatase Shp2. Mol Cell Biol. 2002;22:4062–4072.
- Ke Y, Lesperance J, Zhang EE, et al. Conditional deletion of Shp2 in the mammary gland leads to impaired lobulo-alveolar outgrowth and attenuated Stat5 activation. J Biol Chem. 2006;281:34374–34380.
- Agazie YM, Hayman MJ. Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling. Mol Cell Biol. 2003;23:7875–7886.
- Hanafusa H, Torii S, Yasunaga T, et al. Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. J Biol Chem. 2004;279:22992–22995.
- Xu D, Wang S, Yu WM, et al. A germline gain-of-function mutation in Ptpn11 (Shp-2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells. Blood. 2010;116:3611–3621.
- Lee YS, Ehninger D, Zhou M, et al. Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome. Nat Neurosci. 2014;17:1736–1743.
- Wang S, Yu WM, Zhang W, et al. Noonan syndrome/leukemia-associated gain-of-function mutations in SHP-2 phosphatase (PTPN11) enhance cell migration and angiogenesis. J Biol Chem. 2009;284:913–920.
- Stanford SM1, Maestre MF, Campbell AM, et al. Protein tyrosine phosphatase expression profile of rheumatoid arthritis fibroblast-like synoviocytes: a novel role of SH2 domain-containing phosphatase 2 as a modulator of invasion and survival. Arthritis Rheum. 2013;65(5):1171–1180.
- Gauthier AS, Furstoss O, Araki T, et al. Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. Neuron. 2007;54:245–262.
- Ke Y, Zhang EE, Hagihara K, et al. Deletion of Shp2 in the brain leads to defective proliferation and differentiation in neural stem cells and early postnatal lethality. Mol Cell Biol. 2007;27(19):6706–6717.
- Ehrman LA, Nardini D, Ehrman S, et al. The protein tyrosine phosphatase Shp2 is required for the generation of oligodendrocyte progenitor cells and myelination in the mouse telencephalon. J Neurosci. 2014;34:3767–3778.
- Mohi MG, Williams IR, Dearolf CR, et al. Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell. 2005;7:179–191.
- Dong L, Yu WM, Zheng H, et al. Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment. Nature. 2016;539(7628):304–308.
- Xu D, Liu X, Yu WM, et al. Non-lineage/stage-restricted effects of a gain-of-function mutation in tyrosine phosphatase Ptpn11 (Shp2) on malignant transformation of hematopoietic cells. J. Exp. Med. 2011;208:1977–1988.
- Saba-El-Leil MK, Vella FD, Vernay B, et al. An essential function of the mitogen-activated protein kinase Erk2 in mouse trophoblast development. EMBO Rep. 2003;4:964–968.
- Chen PC, Wakimoto H, Conner D, et al. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome-associated Sos1 mutation. J Clin Invest. 2010;120:4353–4365.
- Guerra C, Mijimolle N, Dhawahir A, et al. Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell. 2003;4(2):111–120.
- Tuveson DA, Shaw AT, Willis NA, et al. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell. 2004;5(4):375–387.
- Hernández-Porras I, Schuhmacher AJ, Garcia-Medina R, et al. K-Ras(V14I)-induced Noonan syndrome predisposes to tumour development in mice. J Pathol. 2016;239(2):206–217.
- Braun BS, Tuveson DA, Kong N, et al. Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci USA. 2004;101(2):597–602.
- Hingorani SR, Petricoin EF, Maitra A, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4(6):437–450.
- Tschaharganeh DF, Lowe SW, Garippa RJ, et al. Using CRISPR/Cas to study gene function and model disease in vivo. FEBS J. 2016;283(17):3194–3203.
- Razzaque MA, Komoike Y, Nishizawa T, et al. Characterization of a novel KRAS mutation identified in Noonan syndrome. Am J Med Genet. 2012;158A:524–532.
- Runtuwene V, van Eekelen M, Overvoorde J, et al. Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects. Dis Model Mech. 2011;4:393–399.
- Jopling C, van Geemen D, den Hertog J. Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects. PLoS Genet. 2007;3:e225.
- Oishi K, Gaengel K, Krishnamoorthy S, et al. Transgenic Drosophila models of Noonan syndrome causing PTPN11 gain-of-function mutations. Hum Mol Genet. 2006;15(4):543–553.
- O’Reilly AM, Pluskey S, Shoelson SE, et al. Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps. Mol Cell Biol. 2000;20:299–311.