普莱克辛B2 (PLXNB2) 中的双变异会导致非完美的乳腺发育,听力损失和智力障碍
Claire E L Smith1, Virginie Laugel-Haushalter2, Ummey Hany3
1Institute of Medical Research, St James's University Hospital, University of Leeds Faculty of Medicine and Health, Leeds, UK bgycels@leeds.ac.uk.
Journal of medical genetics
|March 8, 2024
概括
在plexin B2 (PLXNB2) 中罕见的双变异会导致一种新的自体相衰退综合征. 这种状况的特点是非完善的 amelogenesis 和神经传感器听力损失,具有可变的智力障碍和其他异常.
科学领域:
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 素是细胞相互作用在发育和成年期间至关重要的跨膜半林受体.
- 虽然人类有9个plexin基因,但以前只有PLXND1和PLXNA1变体与孟德尔病有关.
研究的目的:
- 为了研究一种由非完美的乳腺发育和神经传感器听力损失特征的递归遗传综合征的遗传基础.
- 为了识别与这种罕见,表型多样化的疾病相关的新型遗传变异.
主要方法:
- 外基因组或基因组测序对六个家族的八个人进行了测序,这些人患有疑似综合征.
- 根据稀有性,预测功能和自体逆向遗传模式来过变异.
- 通过桑格测序和小鼠RNA表达研究进行了分离分析.
主要成果:
- 在所有家族中,罕见的双性病原体变异在plexin B2 (PLXNB2) 中被确定并与疾病分离.
- 识别的变体包括错误,无意义,拼接和多种类型的删除类型.
- 检测到PLXNB2表达在小鼠的分化乳腺细胞中.
结论:
- 罕见的双性PLXNB2变体会导致一种新型的自体衰退综合征,其中 amelogenesis imperfecta 和感觉神经听力损失作为核心特征.
- 这种综合征呈现出不同的表型,包括智力障碍,眼睛疾病,耳朵异常和淋巴.
- 人类表型与Plxnb2淘汰赛小鼠模型重叠,这可能解释了之前没有报告的人类PLXNB2变异的原因.
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