Most mutations identified in the SMC5 gene are hypomorphic mutations that may or may not affected SMC5 protein expression. The underlying pathophysiological mechanism of disease is an increase in cellular replication stress potentially caused by an inability of cells lacking SMC5 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.
SMC5