Modification of segmental progeroid syndrome phenotypes by the combination of variants of uncertain significance ( VUS ) of DNA repair-related genes
In this study, we presented the possibility that recessive variants showed the phenotype with cooperation or support for other variants effects. The precise mechanisms of DNA repair are complex, involving pathways such as Homologouse Recombination(HR) and Nonhomologouse End Joining(NHEJ) has a relationship with each other. Some components are shared and function redundantly. Even if the effects of variants in individual components are weak, a combination of these effects might reveal distinct phenotypes. We have compared cellular characteristics with clinical data from patients of ten cell lines. The three Segmental Progeroid Syndrome patients, not diagnosed with Werner syndrome (WS), exhibited notable phenotypes and hospitalized. Cell lines of the patients showed typical phenotype of each DNA repair related genes, even each variant was categorized as variants uncertain significance (ACMG class3).