双性PIGM编码变异导致无法治疗的和智力障碍,没有发生血栓事件
Gali Heimer1,2,3, Ben Pode-Shakked2,3,4, Dina Marek-Yagel2,5
1Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Clinical genetics
|October 19, 2024
概括
一种新的PIGM基因变异在兄弟姐妹中导致难以治愈的和智力障碍. 这种基因突变不同于以前识别的PIGM促进子突变,特别是缺乏血栓事件.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 葡萄糖酸酸 (GPI) 生物合成基因越来越多地与婴儿早期脑病变有关.
- 一个先前确定的PIGM促进器突变导致了难以治疗的缺席,智力障碍 (ID) 和血栓事件.
研究的目的:
- 在患有难治性和ID的兄弟姐妹中研究一种新的PIGM基因变异.
- 描述这种新型变种与以前报告的PIGM突变之间的临床和遗传差异.
主要方法:
- 基因测序用于识别PIGM基因中的变异.
- 家庭中的隔离分析.
- 对PIGM蛋白质的结构建模.
- 鉴定变种的功能预测.
主要成果:
- 三个兄弟姐妹呈现了难以治愈的和ID,在PIGM中隐藏了一个同卵性c.224G>A p.
- 这种p.(Arg75His) 变体是进化保守的,罕见的,并预测是有害的,位于PIGM蛋白的敏感区域.
- 与这种编码变体相关的表型不同于PIGM促进子突变,特别是缺乏血栓事件和PIGMcDNA水平或CD59表达的变化.
结论:
- 在PIGM的同卵性p.(Arg75His) 误解变体与一种独特的难治性和ID的表型有关.
- 这一发现扩大了与PIGM相关的疾病的范围,并强调了编码变异在GPI生物合成缺陷中的重要性.
- 由于没有血栓事件,这种编码变异与之前描述的PIGM促进体突变有所区别.
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