Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes (NOLEO)
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|ClinicalTrials.gov Identifier: NCT02486731|
Recruitment Status : Unknown
Verified November 2015 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was: Not yet recruiting
First Posted : July 1, 2015
Last Update Posted : November 9, 2015
Noonan and LEOPARD syndromes share, with variable severity, different clinical traits, notably craniofacial manifestations, cardiopathies, short stature, and juvenile cancers.
The main genetic cause of these syndromes is missense mutation of the gene encoding the ubiquitous tyrosine phosphatase Shp2, found in more than half the patients with NS and in 80% of LS cases. Shp2 plays pivotal roles in development, growth, and metabolism by regulating key signalling pathways (Ras/Mitogen activated protein kinase (MAPK), Phosphoinositide-3 Kinases (PI3K)/Akt) in response to growth factors/hormones. Deregulation of these signalling pathways has been causally linked to NS and LS pathophysiology.
This project aims at better understanding hormonal sensitivity abnormalities in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) caused by mutations of the tyrosine phosphatase Shp2.
To reach this goal, the investigators will take advantage of different tissues (fibroblasts ± adipocytes) from patients with NS / LS compared to healthy controls.
All patients will have a skin biopsy and only patients about to undergo surgery will have a adipose tissue biopsy.
|Condition or disease|
|Noonan Syndrome LEOPARD Syndrome|
The activation of different signaling pathways (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in fibroblasts and/or in adipocytes from patients with NS or LS will be compared to those of healthy subjects.
These data will be correlated to clinical, hormonal, and biochemical characteristics of patients
|Study Type :||Observational|
|Estimated Enrollment :||27 participants|
|Official Title:||Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2018|
Patients with Noonan syndrome
Patients with LEOPARD syndromes
- Phosphorylation of Erk and Akt in fibroblasts [ Time Frame: Baseline ]To evaluate different signaling pathways activation (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in fibroblasts from patients with NS or LS compared to healthy controls
- Phosphorylation of Erk and Akt in adipocytes [ Time Frame: Baseline ]To evaluate different signaling pathways activation (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in adipocytes from patients with NS or LS compared to healthy controls
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02486731
|Contact: Jean Pierre Salles, PU-PHemail@example.com|
|CIC de Toulouse- Unité pediatrique|
|Toulouse, France, 31059|