|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Here, we report a crystal structure of GDP-bound KRAS<sup>V14I</sup>, a mutated KRAS variant associated with the developmental RASopathy disorder Noonan syndrome (NS), at 1.5-1.6 Å resolution.
|
31341022 |
2019 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Gene-related Chinese NS facial features were described using artificial intelligence (AI).NGS identified pathogenic variants in 103 Chinese patients in eight NS-related genes: PTPN11 (48.5%), SOS1 (12.6%), SHOC2 (11.7%), KRAS (9.71%), RAF1 (7.77%), RIT1 (6.8%), CBL (0.97%), NRAS (0.97%), and LZTR1 (0.97%).
|
31219622 |
2019 |
|
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 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We report on an infant with JMML with somatic KRAS G12A mutation and monosomy 7 who achieved sustained remission following azacitidine monotherapy.
|
31250550 |
2019 |
|
Noonan Syndrome
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.
|
29493581 |
2018 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Somatic KRAS mutations are often detected in patients with solid and non-solid tumors, whereas germline KRAS mutations are implicated in patients with the Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome and Costello syndrome.
|
30012129 |
2018 |
|
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 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Juvenile myelomonocytic leukemia in the patient was attributed to a somatic KRAS mutation, whereas the syndromic features of the patient were considered a consequence of germline chromosome 10q22.3-q23.2 deletion.
|
30012129 |
2018 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Recently, six patients with craniosynostosis and Noonan syndrome involving KRAS mutations were described in a review, and a patient with craniosynostosis and Noonan syndrome involving a SHOC2 mutation has also been reported.
|
28650561 |
2017 |
|
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 |
|
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 |
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 |
|
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 |
The final two cases (MYH9 associated macrothrombocytopenia associated with multiple congenital anomalies; atypical juvenile myelomonocytic leukaemia associated with a KRAS mutation) highlight the utility of NGS where the diagnosis is less certain, or where there is an unusual phenotype.
|
25703294 |
2016 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
The inclusion of craniosynostosis as a possible phenotype in KRAS-associated Noonan Syndrome has implications in the differential diagnosis and surgical management of individuals with craniosynostosis.
|
26249544 |
2015 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
CTD_human |
The genomic landscape of juvenile myelomonocytic leukemia.
|
26457647 |
2015 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
RALD has clinical and laboratory features that overlap with those of juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML), including identical somatic mutations in KRAS or NRAS genes noted in peripheral blood mononuclear cells.
|
25691160 |
2015 |
|
Juvenile Myelomonocytic Leukemia
|
1.000 |
Biomarker
|
disease |
BEFREE |
The loss of the wild-type KRAS allele may be a common secondary genetic change in KRAS-related JMML and may affect the differentiation behavior of early JMML progenitors.
|
24766281 |
2015 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
CLINVAR |
Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations.
|
24803665 |
2014 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
MGD |
K-Ras(V14I)-mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML.
|
25359213 |
2014 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
CLINGEN |
K-Ras(V14I)-mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML.
|
25359213 |
2014 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
CLINVAR |
Tegumentary manifestations of Noonan and Noonan-related syndromes.
|
24037001 |
2013 |
|
Noonan Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A lethal course of hypertrophic cardiomyopathy in Noonan syndrome due to a novel germline mutation in the KRAS gene: case study.
|
24382853 |
2013 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
The RASopathies.
|
23875798 |
2013 |
|
Noonan Syndrome
|
1.000 |
Biomarker
|
disease |
CLINGEN |
Here we report on a case of an infant with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy with lethal outcome, in whom we identified a novel mutation in the KRAS gene.
|
24382853 |
2013 |