Whole-Exome Sequencing Followed by dPCR-Based Personalized Genetic Approach in Solid Organ Transplantation: A Study Protocol and Preliminary Results

Genetic profiling and molecular biology methods have made it possible to study the etiology of the end-stage organ disease that led to transplantation, the genetic factors of compatibility and tolerance of the transplant, and the pharmacogenetics of immunosuppressive drugs and allowed for the development of monitoring methods for the early assessment of allograft rejection. This study aims to report the design and baseline characteristics of an integrated personalized genetic approach in solid organ transplantation, including whole-exome sequencing (WES) and the monitoring of dd-cfDNA by dPCR. Preliminary results reported female recipients with male donors undergoing two pediatric and five adult kidney and three heart transplantations. WES revealed a pathogenic mutation in <i>RBM20</i> and VUS in <i>TTN</i> and <i>PKP2</i> in heart recipients, while kidney donors presented mutations in <i>UMOD</i> and <i>APOL1</i> associated with autosomal-dominant kidney diseases, highlighting the risks requiring the long-term monitoring of recipients, donors, and their family members. %dd-cfDNA levels were generally stable but elevated in cadaveric kidney recipient and one pediatric patient with infectious complications and genetic variants in the <i>ABCB1</i> and <i>ABCC2</i> genes. These findings highlight the potential of combining genetic and molecular biomarker-based approaches to improve donor-recipient matching, predict complications, and personalize post-transplant care, paving the way for precision medicine in transplantation.