It should be investigated in the future at which extent this defect, if confirmed in all CS patients, is correlated with and participates to the severity of the disease, whether CSA is implicated in the same pathway as CSB, and also whether it is operating in UVSS patients that lack the progeroid phenotype and whose cells do not display the HTRA3/POLG1/mitochondrial defect22. This evidence concerns the gene POLG and Cowden syndrome 1.