Most mutations identified in the SLF2 gene are inactivating mutations leading to a loss or reduction in SLF2 protein expression. The underlying pathophysiological mechanism of disease is an increase in cellular replication stress potentially caused by an inability of cells lacking SLF2 to deal with naturally occurring replication impediments e.g. G-quadruplexes and topological abnormalities in the DNA. Cytologically, cells from Atelís syndrome patients characteristically exhibit mosaic variegated hyperploidy, segmented chromosomes and partial cohesion defects.
SLF2