|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Studies have shown that NSML-associated Y279C mutation exhibited the reduced phosphatase activity, leading to loss-of-function (LOF) of SHP2.
|
31258001 |
2019 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase Shp2, cause Noonan syndrome and LEOPARD syndrome, inherited multifaceted diseases including cardiac and vascular defects.
|
31634485 |
2019 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Although PTPN11 mutation showed initially positive regulation on phosphoinositide 3-kinase, overall the mTOR complex 1 pathway showed widely attenuated activity in LS.
|
31722741 |
2019 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A human induced pluripotent stem cell (iPSC) line was generated using peripheral blood mononuclear cells (PBMCs) from a patient with NSML that carries a gene mutation of p.Q510P on the PTPN11 gene using non-integrating Sendai virus technique.
|
30640061 |
2019 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Different mechanisms of disease have been demonstrated to be associated with the two classes of PTPN11 mutations underlying Noonan syndrome and Noonan syndrome with multiple lentigines (also known as LEOPARD syndrome).
|
31277675 |
2019 |
|
LEOPARD Syndrome
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.
|
29493581 |
2018 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Catalytically activating mutations in <i>Ptpn11</i>, which encodes the protein tyrosine phosphatase SHP2, cause 50% of Noonan syndrome (NS) cases, whereas inactivating mutations in <i>Ptpn11</i> are responsible for nearly all cases of the similar, but distinct, developmental disorder Noonan syndrome with multiple lentigines (NSML; formerly called LEOPARD syndrome).
|
29559584 |
2018 |
|
LEOPARD Syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K.
|
29084544 |
2017 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The present study describes four NS patients and one NSML patient with a PTPN11 mutation.
|
28483241 |
2017 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We previously generated a transgenic mouse model of NSML-associated HCM induced by Q510E-SHP2 expression in cardiomyocytes starting before birth.
|
28911943 |
2017 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The present study reports a young child diagnosed with LS via identification of a common p.Thr468Met mutation in PTPN11.
|
27484170 |
2016 |
|
LEOPARD Syndrome
|
1.000 |
Biomarker
|
disease |
BEFREE |
Comparisons between clinical presentations showed that SASH1-related phenotypes can exhibit hyper- and hypopigmentation on the trunk and extremities, similar to dyschromatosis, while scattered café au-lait spots usually appeared in PTPN11-related LEOPARD syndrome.
|
27659786 |
2016 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We report a patient with Noonan syndrome with multiple lentigines (NSML) due to a PTPN11 (p.Thr468Met) mutation associated with hypertrophic neuropathy of lumbar plexus in an adult woman, initially referred for neuropathic pain.
|
26952712 |
2016 |
|
LEOPARD Syndrome
|
1.000 |
Biomarker
|
disease |
CLINGEN |
We report a patient with Noonan syndrome with multiple lentigines (NSML) due to a PTPN11 (p.Thr468Met) mutation associated with hypertrophic neuropathy of lumbar plexus in an adult woman, initially referred for neuropathic pain.
|
26952712 |
2016 |
|
LEOPARD Syndrome
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin.
|
26742426 |
2016 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Phenotypical diversity of patients with LEOPARD syndrome carrying the worldwide recurrent p.Tyr279Cys PTPN11 mutation.
|
26377839 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
In in vitro assays, melanin synthesis in human melanoma cells expressing SHP-2 with LS-associated mutations was higher than in cells expressing normal SHP-2, suggesting that LS-associated SHP-2 mutations might enhance melanin synthesis in melanocytes, and that the activation of Akt/mTOR signalling may contribute to this process.
|
25917897 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain.
|
25884655 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Exome sequencing revealed a pathogenic de novo germline variant in the PTPN11 gene (c.1529A>G; p.(Gln510Arg)), which has so far been associated with Noonan, as well as LEOPARD syndrome.
|
24939587 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In the boy, progressive HCM was diagnosed during the first week of life and a diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in PTPN11.
|
25708222 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Moreover, human activating and inactivating mutations of SHP2 are responsible for two related developmental disorders called Noonan and LEOPARD Syndromes, respectively, which are both characterized, in part, by congenital heart defects.
|
25256404 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
Biomarker
|
disease |
CLINGEN |
In in vitro assays, melanin synthesis in human melanoma cells expressing SHP-2 with LS-associated mutations was higher than in cells expressing normal SHP-2, suggesting that LS-associated SHP-2 mutations might enhance melanin synthesis in melanocytes, and that the activation of Akt/mTOR signalling may contribute to this process.
|
25917897 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We hereby report a heterozygous de novo mutation in the PTPN11 gene (c.1403C > T) manifesting with a clinical picture of LS during childhood, and later development of neuropathic pain with hypertrophic plexi, which are typically observed in NF1 but have not been reported in LS.
|
25884655 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In the second part, we describe the different PTPN11 mutation-associated pathologies and their clinical manifestations, with particular focus on the biochemical and signaling outcomes of NS and NS-ML-associated mutations, and on the recent advances regarding the pathophysiology of these diseases.
|
26341048 |
2015 |
|
LEOPARD Syndrome
|
1.000 |
CausalMutation
|
disease |
CLINVAR |
LEOPARD syndrome: clinical dilemmas in differential diagnosis of RASopathies.
|
24767283 |
2014 |