Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Phosphorylation of Erk and Akt in fibroblasts
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 5 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with Noonan syndrome (NS) or LEOPARD syndrome (LS):
- •female or male
- •age between 5 to 15 years
- •clinical diagnosis of NS or LS according to published criteria
- •signed informed consent of parents
- •Healthy controls:
- •female or male
- •age between 5 to 15 years
- •no personal history of syndrome or chronic disease
- •planned surgical procedure
- •signed informed consent of parents
排除标准
- •age below 5 or above 15 years
- •pregnancy
- •In healthy controls: syndromic or chronic disease
结局指标
主要结局
Phosphorylation of Erk and Akt in fibroblasts
时间窗: 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
次要结局
- Phosphorylation of Erk and Akt in adipocytes(Baseline)