NSMCE2 and Andersen-Tawil syndrome: Notably MEFs derived from the Nsmce2 knockout mice exhibited increased spontaneous replication stress and genome instability due to a failure to detangle recombination intermediates similar to ATS patient cell lines (e.g., elevated levels of BRCA1 foci, increased sister chromatid and telomeric SCEs and chromosomal segregation errors)65 indicating that ATS represents a more severe form of SMC5/6 dysfunction.