与desmoplakin相关的棕植物表皮分化障碍:一个独特的表型和心肌病症的红旗
Eveliina Brandt1, Krista Heliö2, Liisa Harjama1
1Department of Dermatology and Allergology, ERN-Skin center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Clinical and experimental dermatology
|October 18, 2025
概括
异合性德斯莫普拉金 (DSP) 变种导致早期发病的棕植物表皮分化障碍 (pEDD),这些障碍在几十年之前发生了心律失常心肌病. 对于患有pEDD的患者来说,基因检测至关重要,对于DSP变异携带者来说,心脏评估至关重要.
科学领域:
- 心血管医学 心血管医学
- 皮肤病学 皮肤病学
- 遗传学 遗传学 是一个
背景情况:
- 致病性异性德斯莫普拉金 (DSP) 变体与心律失常心肌病变和心脏突然死亡有关.
- 这些DSP变体也在皮肤病患者中发现,这些患者患有棕植物表皮分化障碍 (pEDD) 和特定的头发状况.
- 在DSP中具有不确定的意义的变异 (VUS) 复杂化了pEDD患者的心脏风险评估.
研究的目的:
- 为了描述与异构性DSP变体相关的心皮表型.
- 调查DSP变体,pEDD和心肌病发育之间的关系.
- 为了澄清DSP变异的临床影响,包括VUS,在受影响的个体中.
主要方法:
- 从18个家族中招收了45个异构体DSP载体和10个非载体.
- 进行遗传评估,包括下一代测序,整个外基因组或桑格测序.
- 进行了全面的心脏 (心电图,心声学,MRI) 和皮肤学 (皮肤组织学,头发显微镜) 评估.
主要成果:
- 确定了17种DSP变异 (10种致病性/可能致病性,7种VUS),其中15种与pEDD相关.
- 在86%的携带者中观察到特征性焦点皮炎,以及其他pEDD特征和卷发/波浪发.
- 在72%的携带者中发现心脏异常,其中60%符合心肌病标准,44%经历心律失常;VUS显示了类似的表型.
结论:
- 异构性DSP变体会导致童年发病的焦点PEDD,然后是中年发病的失律性心肌病变.
- 在心脏异常变得明显之前,pEDD的发病通常会在几十年内发生.
- 在pEDD患者中,对DSP变异的基因检测至关重要,对所有DSP变异携带者来说,心脏评估至关重要.
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