Histone 3.3-related chromatinopathy: missense variants throughout H3-3A and H3-3B cause a range of functional consequences across species

AbstractThere has been considerable recent interest in the role that germline variants in histone genes play in Mendelian syndromes. Specifically, missense variants inH3-3A andH3-3B, 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.

Source: Human Genetics - March 3, 2023 Category: Genetics & Stem Cells Source Type: research