BMPR1a疾病的基因型-表型相关性导致青少年多发症综合征变异
M E Papadopulos1,2, J P Plazzer3, F A Macrae4,3
1Department of Medicine, University of Melbourne, The Royal Melbourne Hospital, Melbourne, Australia. mariepapadopulos98@gmail.com.
Hereditary cancer in clinical practice
|July 3, 2023
概括
与BMPR1a变体相关的青少年多发症综合征 (JPS) 主要影响结肠和直肠. 这表明在BMPR1a载体中针对结直肠多和恶性瘤进行有针对性的监测,可能排除胃查.
科学领域:
- 遗传学和基因组学 在
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
背景情况:
- 青少年多发症综合征 (JPS) 是一种自体主导性疾病,其特征是型多发症和胃肠道癌症风险增加.
- 在45-60%的JPS病例中,BMPR1a或SMAD4基因的致病变体 (DCV) 被确定,其中BMPR1a变体占17-38%.
- 在患有BMPR1a或SMAD4DCV的JPS患者中存在显著的表型变异性,包括息肉位置,恶性瘤风险和胃肠外表现.
研究的目的:
- 调查BMPR1a.中的基因-表型关联和基因型-表型相关性.
- 为JPS患有BMPR1a变异的患者提供监测建议.
- 为了完善美国医学遗传学和基因组学学院 (ACMG) 的BMPR1aDCVs的分类.
主要方法:
- 在EMBASE,MEDLINE和PubMed中进行全面的文献搜索.
- 包括关于BMPR1a与DCV相关的JPS和相连的PTEN和BMPR1a删除的研究.
- 从BMPR1a特定的数据库提取数据,包括LOVD和ClinVar.
主要成果:
- 确定了211个BMPR1aDCV,其中82个来自JPS患者,17个来自LOVD,112个来自ClinVar.
- 变种包括错误,无意义,框架转移和所有基因功能领域的大型删除类型.
- 与SMAD4携带者不同,BMPR1a携带者主要表现出结肠多重症和恶性瘤;BMPR1a携带者没有观察到胃多重症/恶性瘤.
- 根据BMPR1a.内的变异类型或功能域,没有建立特定的基因型-表型相关性.
结论:
- BMPR1a变体的位置与特定的表型特征无关.
- BMPR1a DCVs的主要结直肠表现有助于病原性评估.
- 对BMPR1aDCV载体的监测应侧重于结直肠聚和恶性瘤,可能认为胃查不必要.
- 目前的数据不支持基于BMPR1a.内的变异位置的差异监测建议.
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