分子基础和诊断方法对儿童中孤立和综合征侧面过度生长
Simone Bellucca1, Diana Carli2, Andrea Gazzin3
1Postgraduate School of Pediatrics, University of Torino, Turin, Italy.
The Journal of pediatrics
|June 30, 2024
概括
一个新的分子诊断工作流实现了54%的横向过度生长 (LO) 的诊断率,这是一种先天性疾病. 这种方法有助于对LO亚型进行分类,并改善患者管理.
科学领域:
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
- 遗传性疾病 遗传性疾病
背景情况:
- 横向过度生长 (LO) 是一种先天性疾病,其特点是身体部位异常膨胀.
- 精确的分子遗传LO的分类对于理解其病因和指导管理至关重要.
- 目前的LO诊断方法缺乏标准化的分子遗传指导方针,导致诊断不足.
研究的目的:
- 为横向过度生长 (LO) 建立一个高收益的分子诊断工作流.
- 根据遗传基础分子分类LO病例.
- 为了改善先天性过度生长条件的诊断产量.
主要方法:
- 追溯将186个LO病例 (2003-2023) 分类为疑似综合征 (贝克威斯-维德曼谱,与PIK3CA相关的过度生长谱,血管过度生长,孤立的LO).
- 使用血液或皮肤DNA,针对PI3K/AKT/mTOR,血管增殖和RAS-MAPK通路中的11p15异常和体变异的向分子测试.
- 对最初负结果的病例实施顺序级联分子方法.
主要成果:
- 该工作流实现了LO的54%的分子诊断率.
- 89%的诊断符合最初的临床怀疑,11%的诊断被重新分类.
- 经常发现贝克威斯-维德曼谱系 (43%具有11p15异常) 和与PIK3CA相关的过度生长谱系 (74%确认率).
结论:
- 横向过度生长在分子层面上被低诊断,需要标准化的诊断指南.
- 量身定制的分子诊断方法对于在LO中实现高诊断产量至关重要.
- 精确的分子分类使精准医学,癌症风险评估和优化患者管理成为可能.
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