Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Hum Genet. 2024 Apr;143(4):497-510. doi: 10.1007/s00439-023-02536-2. Epub 2023 Mar 3.
There has been considerable recent interest in the role that germline variants in histone genes play in Mendelian syndromes. Specifically, missense variants in H3-3A and H3-3B, which both encode Histone 3.3, were discovered to cause a novel neurodevelopmental disorder, Bryant-Li-Bhoj syndrome. Most of the causative variants are private and scattered throughout the protein, but all seem to have either a gain-of-function or dominant negative effect on protein function. This is highly unusual and not well understood. However, there is extensive literature about the effects of Histone 3.3 mutations in model organisms. Here, we collate the previous data to provide insight into the elusive pathogenesis of missense variants in Histone 3.3.
近年来，人们对组蛋白基因中的种系变异在孟德尔综合征中的作用产生了浓厚的兴趣。具体来说，编码组蛋白 3.3 的 H3-3A 和 H3-3B 中的错义变异被发现会导致一种新的神经发育障碍，即 Bryant-Li-Bhoj 综合征。大多数致病变异是私有的，分布在整个蛋白质中，但似乎都对蛋白质功能具有获得性功能或显性负效应。这是非常不寻常的，也不太理解。然而，关于组蛋白 3.3 突变在模式生物中的影响有大量文献。在这里，我们整理了以前的数据，以深入了解组蛋白 3.3 中错义变异的难以捉摸的发病机制。
