NCT02486731

Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes

Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 27 (actual)
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France · Other Government
• Sex: All
• Age: 5 Years – 15 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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

Conditions

• Noonan Syndrome
• LEOPARD Syndrome

Timeline

• Start date: 2015-12-16
• Primary completion: 2018-12-01
• Completion: 2018-12-01
• First posted: 2015-07-01
• Last updated: 2021-08-26

Locations

1 site across 1 country: France