Results of Sequencing of a Large Panel of Genes From Leptin Melanocortin Pathway in Children Suffering From Severe Obesity
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 主要终点
- frequency of mutations of genes from leptin melanocortin pathway
研究概览
简要总结
About 380 million children and adolescents suffer from overweight and obesity at the global level. Obesity results from the interplay between biological (sex, age, fetal programming, gut microbiota, epigenetics, and genetics) and environmental factors (e.g., unhealthy diet, physical inactivity, stress). Mutations in genes from leptin melanocortin pathway are involved in "non syndromic monogenic obesity", characterized by severe early onset obesity, hyperphagia and endocrine deficiencies. Exact frequencies of mutation in these genes are not precisely evaluated in french children with severe obesity. Moreover new treatment, such seltmelanotide are avalaible in case of certain mutation, leading to a significative weight loss in treated patients.
详细描述
Obesity is a global health concern that affected more than 650 million adult people and more than 380 million children and adolescents worldwide, with no signs of slowing down despite major investments in health policy. Obestiy is a multifactorial disease, but 40 to 75% of body mass index (BMI) variation is explained by genetic factors.
Mutations in genes from leptin melanocortin pathway lead to "non syndromic monogenic obesity", characterized by severe early onset obesity, hyperphagia and endocrine deficiencies. This pathway plays a central role in regulating mammalian food intake, energy expenditure and body weight regulation. Somes genes are well characterized such LEP gene, LEPR gene, or MC4R but others have been recently described as ADCY3, SIM1, SH2B1, NTRK2, BDNF, KSR2.
The frequency of these mutations are not precisely estimated in a group of french children with severe obesity.
Moreover, a precocious identification of these mutations, could afford, in certain case the possibility of a efficient treatment with setmelanotide, leading to a significant weight loss in treated patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •severe obesity with BMI > 3SDS
排除标准
- •genetic obesity (Prader Willi syndrome, Bardet Biedl syndrome, X fragile syndrome, Alstrom syndrome)
- •BMI < 3 SDS
- •age < 6 months
- •monogenic non syndromic obesity, with mutation in genes of leptin melanocortin pathway previously diagnosed
- •cushing syndrome
研究组 & 干预措施
severe obese children
children with severe obesity with BMI > 3sds
干预措施: sequencing of a panel of 14 genes in leptin melanocortin pathway (Genetic)
结局指标
主要结局
frequency of mutations of genes from leptin melanocortin pathway
时间窗: 1 year
Evaluating of the frequency of mutations of 14 genes from leptin melanocortin pathway (LEP, LEPR, POMC, PCSK1, MC3R, MC4R, MRAP2, ADCY3, SIM1, SH2B1, NTRK2, BDNF, KSR2) in a group of french children with severe obesity.
次要结局
- Clinical characteristics of children with severe obesity followed in CHRU of Nancy(1 year)
- Clinical characteristics of children with mutations of leptin melanocortin pathway(1 year)
- Penetrance of mutations from leptin melanocortin pathway(1 year)
- effect of age, sex, country of birth on mutations' penetrance.(1 year)
研究者
RENARD Emeline
Doctor
Central Hospital, Nancy, France