|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Yet, the malignancy risk in CS is notably higher than in Noonan syndrome with a KRAS mutation.
|
26572961 |
2016 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Mutations of PTPN11, KRAS and SOS1 in the RAS-MAPK pathway cause approximately 60% of cases of Noonan syndrome.
|
17603482 |
2007 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
We analyzed PTPN11 and KRAS genes by bidirectional sequencing in 95 probands with NS and 29 with Noonan-like syndromes, including previously reported patients already screened for PTPN11 gene mutations.
|
20578946 |
2010 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Mutations in PTPN11 and KRAS have been identified in patients with NS and those in KRAS, BRAF and MAP2K1/2 have been identified in patients with CFC syndrome, establishing a new role of the RAS/MAPK pathway in human development.
|
18651097 |
2008 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The scope of cardiac disease in Noonan syndrome is quite variable depending on the gene mutation, with some mutations usually associated with a high incidence of congenital heart defects (PTPN11, KRAS, and others) while those with predominantly hypertrophic cardiomyopathy (HCM) have higher risk and morbidity profiles (RAF1, RIT1, and those associated with multiple lentigines).
|
30024444 |
2018 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We have previously developed and characterized a knock-in mouse model that carries one of the most frequent KRAS-NS-related mutations, the K-Ras(V14I) substitution, which recapitulates most of the alterations described in NS patients, including MPDs.
|
27174785 |
2016 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.
|
16474405 |
2006 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We performed detailed biochemical and functional studies of three mutant K-Ras proteins (P34R, D153V, and F156L) found in individuals with Noonan syndrome and cardiofaciocutaneous syndrome.
|
17875937 |
2007 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder that is phenotypically similar to Noonan syndrome and is associated with mutations in BRAF, MEK1, MEK2, and KRAS.
|
31125963 |
2019 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The discovery of KRAS missense mutation as a minor cause of Noonan syndrome and the pathogenetic mechanisms of those mutants is discussed.
|
16987887 |
2006 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Our findings implicate that N116S change in KRAS is a hyperactive mutation which is a causative agent of NS through maldevelopment of the heart.
|
22302539 |
2012 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown.
|
17143285 |
2007 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases.
|
17603483 |
2007 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutations in KRAS, HRAS, and other genes coding for proteins participating in this signaling cascade have recently been identified as underlying Noonan syndrome (NS) and related disorders.
|
19396835 |
2009 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We report a patient with Noonan syndrome and a novel KRAS mutation who presents systemic lupus erythematosus.
|
20810036 |
2010 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
RASopathies (Noonan syndrome (NS) and Noonan-related syndromes) are neurodevelopmental syndromes resulting from germline mutations in genes that participate in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway (PTPN11, SOS1, RAF, KRAS or NRAS, and SHOC2).
|
23786871 |
2013 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Finally, we found that primary cells from a patient with KRAS-mutant juvenile myelomonocytic leukemia displayed reduced colony formation in response to JAK2 inhibition.
|
27418650 |
2016 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, we identified 4 (18.2%) NRAS mutations and 1 (4.5%) KRAS mutation in 5 JMML samples, 1 of which had a concomitant PTPN11 mutation.
|
16518851 |
2006 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These data indicate that SHIP-1 can effectively block GM-CSF hypersensitivity in JMML progenitor cells with mutations in KRAS2 or PTPN11 and may be a useful approach for the treatment of JMML patients.
|
17268534 |
2007 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In this report, we describe a case of JMML with blastic transformation possibly caused by additional copy number gains of the KRAS mutant allele.
|
28244637 |
2017 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis.
|
17332249 |
2007 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
On the basis of the clinical suspicion of NS, mutation analysis revealed a KRAS mutation, which is known to be common to both NS and JMML.
|
22510777 |
2012 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
BEFREE |
We demonstrated that duplication of oncogenic KRAS is associated with rapid JMML progression.
|
23403250 |
2013 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
BEFREE |
Mutations in NF1, PTPN11, NRAS, KRAS and CBL have been reported to play a pathogenetic role in juvenile myelomonocytic leukaemia (JMML), a rare myelodyplastic/myeloproliferative neoplasm occurring in children.
|
20408841 |
2010 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Juvenile myelomonocytic leukemia (JMML) is an intractable pediatric leukemia with poor prognosis whose molecular pathogenesis is poorly understood, except for somatic or germline mutations of RAS pathway genes, including PTPN11, NF1, NRAS, KRAS and CBL, in the majority of cases.
|
23832011 |
2013 |