Molecular Etiology and Epigenetic Landscape of Rahman Syndrome – RAHMAN

Germline frameshift mutations in one of the alleles of the linker histone H1E were causally linked to an as-yet poorly defined syndrome, called Rahman syndrome. Affected individuals exhibit characteristic craniofacial features, hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Limited epigenomic data available on Rahman syndrome patients indicate that the H1E mutations may affect the overall epigenetic landscape of chromatin and several vital nuclear processes, including cell division. Here, we will use a unique combination of powerful structural and epigenomic profiling approaches coupled to cutting-edge molecular and cell biology techniques, including CRISPR/CAS technology, to dissect the origin and evolution of the Rahman syndrome at the molecular level. This work is expected to reveal the intimate mechanism of the detrimental effect of the H1E mutant on chromosome segregation and cell division.