Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

Nature Genetics

Volumn 39, Issue 8, 2007, Pages 1007-1012

  Pandit, Bhaswati ^a   Sarkozy, Anna ^b,c   Pennacchio, Len A ^d,e   Carta, Claudio ^f   Oishi, Kimihiko ^a   Martinelli, Simone ^f   Pogna, Edgar A ^f   Schackwitz, Wendy ^d,e   Ustaszewska, Anna ^d   Landstrom, Andrew ^g   Bos, J Martijn ^g   Ommen, Steve R ^g   Esposito, Giorgia ^b,c   Lepri, Francesca ^b,c   Faul, Christian ^a   Mundel, Peter ^a   López Siguero, Juan P ^h   Tenconi, Romano ⁱ   Selicorni, Angelo ^j   Rossi, Cesare ^k   Mazzanti, Laura ^k   Torrente, Isabella ^b   Marino, Bruno ^c   Digilio, Maria C ^l   Zampino, Giuseppe ^m   Ackerman, Michael J ^g   Dallapiccola, Bruno ^b,c   Tartaglia, Marco ^a,f   Gelb, Bruce D ^a   more..

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b Ospedale CSS San Giovanni Rotondo   (Italy)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

^d LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^e DOE JOINT GENOME INSTITUTE   (United States)

^f ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^g Mayo Clinic   (United States)

^h HOSPITAL MATERNO INFANTIL   (Spain)

ⁱ UNIVERSITY OF PADOVA   (Italy)

^j UNIVERSITY OF MILAN   (Italy)

^k UNIVERSITY OF BOLOGNA   (Italy)

^l BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^m CATHOLIC UNIVERSITY   (Italy)

more..

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; PHOSPHOTRANSFERASE; SOS PROTEIN;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; ENZYME ACTIVATION; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC CODE; HUMAN; HUMAN CELL; HYPERTROPHIC CARDIOMYOPATHY; INHIBITION KINETICS; LEOPARD SYNDROME; MAJOR CLINICAL STUDY; MISSENSE MUTATION; NOONAN SYNDROME; ONCOGENE RAS; PATHOGENESIS; PREVALENCE; PRIORITY JOURNAL; PTPN11 GENE; RAF1 GENE;

EID: 34547530823     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng2073     Document Type: Article

References (30)

1. Carta, C. et al. Germline missense mutations affecting KRAS isoform B are associated with a severe Noonan syndrome phenotype. Am. J. Hum. Genet. 79, 129-135 (2006).
2. Kontaridis, M.I., Swanson, K.D., David, F.S., Barford, D. & Neel, B.G. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J. Biol. Chem. 281, 6785-6792 (2006).
3. Schubbert, S. et al. Germline KRAS mutations cause Noonan syndrome. Nat. Genet. 38, 331-336 (2006).
4. Tartaglia, M. et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat. Genet. 29, 465-468 (2001).
5. Roberts, A.E. et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat. Genet. 39, 70-74 (2007).
6. Tartaglia, M. et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat. Genet. 39, 75-79 (2007).
7. Digilio, M.C. et al. Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 Gene. Am. J. Hum. Genet. 71, 389-394 (2002).
8. Aoki, Y. et al. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat. Genet. 37, 1038-1040 (2005).
9. Niihori, T. et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat. Genet. 38, 294-296 (2006).
10. Rodriguez-Viciana, P. et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science 311, 1287-1290 (2006).
11. Tartaglia, M. et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am. J. Hum. Genet. 78, 279-290 (2006).
12. Tartaglia, M. et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am. J. Hum. Genet. 70, 1555-1563 (2002).
13. Burch, M. et al. Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients. J. Am. Coll. Cardiol. 22, 1189-1192 (1993).
14. Van Driest, S.L. et al. Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 44, 1903-1910 (2004).
15. Wellbrock, C., Karasarides, M. & Marais, R. The RAF proteins take centre stage. Nat. Rev. Mol. Cell Biol. 5, 875-885 (2004).
16. Emuss, V., Garnett, M., Mason, C. & Marais, R. Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF. Cancer Res. 65, 9719-9726 (2005).
17. Zebisch, A. et al. Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Cancer Res. 66, 3401-3408 (2006).
18. Greenman, C. et al. Patterns of somatic mutation in human cancer genomes. Nature 446, 153-158 (2007).
19. Muslin, A.J., Tanner, J.W., Allen, P.M. & Shaw, A.S. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 84, 889-897 (1996).
20. Light, Y., Paterson, H. & Marais, R. 14-3-3 antagonizes Ras-mediated Raf-1 recruitment to the plasma membrane to maintain signaling fidelity. Mol. Cell. Biol. 22, 4984-4996 (2002).
21. Wan, P.T. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855-867 (2004).
22. Muslin, A.J. Role of raf proteins in cardiac hypertrophy and cardiomyocyte survival. Trends Cardiovasc. Med. 15, 225-229 (2005).
23. Bueno, O.F. et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 19, 6341-6350 (2000).
24. Hunter, J.J., Tanaka, N., Rockman, H.A., Ross, J. Jr. & Chien, K.R. Ventricular expression of a MLC-2v-ras fusion gene induces cardiac hypertrophy and selective diastolic dysfunction in transgenic mice. J. Biol. Chem. 270, 23173-23178 (1995).
25. Gripp, K.W. et al. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am. J. Med. Genet. A. 140, 1-7 (2006).
26. Yamaguchi, O. et al. Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis. J. Clin. Invest. 114, 937-943 (2004).
27. Patel, R. et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation 104, 317-324 (2001).
28. Sarkozy, A. et al. Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. J. Med. Genet. 41, e68 (2004).
29. Ucar, C., Calyskan, U., Martini, S. & Heinritz, W. Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). J. Pediatr. Hematol. Oncol. 28, 123-125 (2006).
30. Merks, J.H., Caron, H.N. & Hennekam, R.C. High incidence of malformation syndromes in a series of 1,073 children with cancer. Am. J. Med. Genet. A. 134, 132-143 (2005).