Clinical exome sequencing identified POLB c.C1002A as a possible genetic cause in a family with hereditary cancer-predisposing syndrome.

This study recruited a Chinese family with hereditary cancer-predisposing syndrome. To investigate the causative mutations, disease-associated exome sequencing was conducted using peripheral blood of three members with malignant disease. As a result, three variants (PLD2 c. C1951T, RAB3GAP1 c.A701G and POLB c.C1002A) came out to be the potential candidate pathogenic mutations, which were not reported before. Sanger sequencing was used to validate the candidate variant in seven healthy members of this family. The candidate variant POLB c.C1002A was proved to co-segregate with malignant diseases, which was selected through a series of filtering criteria. This study thus identified POLB c.C1002A as a potential causative variant for hereditary cancer-predisposing syndrome.