Investigation of the Genetic Architecture of Linear Localized Scleroderma (LLS) (Linear Morphea) by Whole Exome Sequencing. A Tailored Approach to Test the Hypothesis That LLS is a Genetic Mosaic Condition
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- number of key genes /number of mutations in LLS (localized linear scleroderma)
研究概览
简要总结
The purpose of this study is to investigate the genetic architecture of Linear Localized Scleroderma (LLS) (linear morphea) by whole exome sequencing.
详细描述
At present the etiology of LLS is unknown, but a genetic background is suspected. Although LLS clearly classifies as a mosaic disorder, its genetics and protein machinery remain to be understood.
We are going to use a tailored approach to identify the genetic factors of LLS. In the first phase of the study we will investigate the genetic architecture in LLS. WES will analyze whole protein coding DNA in skin samples of 50 consenting LLS patient. The aim is to identify the key genes associated with LLS. In the second phase of the study subsequent functional experiments will be performed. Based on the identified candidate genes, knockdown and overexpression models will be created with relevant cell lines (fibroblasts) to identify the biological consequences and confirm the functional relevance of the identified genetic mutations in LLS. Further the protein network active in LLS will be investigated (proteomic analysis).
The described basic genetic studies combined with functional experiments will lay the groundwork for treatment trials to provide possibly novel treatment options.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects ≥ 5 years of age with well phenotyped LLS
- •Affecting their head and / or face "termed " en coup de sabre " type LLS or Hemiatrophia faciei or Parry-Romberg syndrome, with or without therapy
- •Affecting any site of the body except the head or face, with or without therapy
排除标准
- •Patients with signs of systemic scleroderma
- •Patients with localized scleroderma (morphea) other than the linear type ("plaque-type", "morphea profunda", "generalized morphea") Patients with diagnosed gadolinium induced scleroderma Patients with post-irradiation scleroderma Patients with missing consent
结局指标
主要结局
number of key genes /number of mutations in LLS (localized linear scleroderma)
时间窗: 24-30 months
次要结局
- the investigation of the protein network of the identified key genes in order to assess their biological function and their relevance in the pathogenesis of LLS.(24-30 months)