Tremblay MW, Green MV, Goldstein BM, Aldridge AI, Rosenfeld JA, Streff H, Tan WD, Craigen W, Bekheirnia N, Al Tala S, West AE, and Jiang YH.
Human Molecular Genetics, 2021.
Scientists use bioelectronic assays to explore neuronal dysfunction associated with Rahman syndrome
Rahman syndrome is a rare genetic neurodevelopmental disorder associated with intellectual disability, distinctive facial features, bone and vision abnormalities, anxiety, and autism spectrum disorder. Research has shown that Rahman syndrome is caused by mutations in the histone linker gene H1-4, which results in an H1-4 protein with an abnormal C-terminus frameshifted tail (H1.4 CFT), but the underlying mechanisms of brain impairment related to the disorder are not fully understood. In this study, scientists identify new variants of H1.4 and characterize their transcriptional and functional effects in neurons.
To assess neuronal activity, the researchers used Axion’s Maestro multielectrode array (MEA) platform to study rat hippocampal neurons. Findings revealed that neurons expressing H1.4 CFT showed significantly lower levels of firing and reduced synchrony compared to controls, demonstrating for the first time that H1.4 CFT disrupts neuronal physiology.
Taken together with other results, the authors conclude that the study provides novel insights into the causes of neurodevelopmental impairments associated with frameshift mutations in the C-terminus of H1.4 and suggest that additional research is needed to better understand the function of histone H1.4 in neurons.