Genetic Insights through Chinese VTE Pedigree Interpretation Using the ACMG Method: Unraveling Potencial Genetic Risk Factors

<bold>Aim:</bold> The study aims to bridge existing gaps in understanding VTE genetics by focusing on familial units with unexplained VTE occurrences. <bold>Methodology:</bold> Participant Selection: Identify and recruit individuals from 9 Chinese pedigrees with a clear family history of VTE. Employ high-throughput whole-genome sequencing (WGS) technology for comprehensive genetic analysis. Utilize the American College of Medical Genetics and Genomics (ACMG) scoring system for variant interpretation and familial analysis. <bold>Result:</bold> We successfully identified and interpreted 10 variants directly linked to thrombosis through harmful mutation filtering and VTE-specific ACMG rating, which enabled the interpretation of thrombotic risk in 8 pedigree, shedding light on the elusive genetic underpinnings of VTE within these cohorts. Moreover, our investigation revealed notable risk mutations within the ADAMTSs gene family associated with thrombosis susceptibility across multiple families, completing the interpretation of all pedigrees. <bold>Conclusion:</bold> By applying the ACMG scoring system and evidence-based medicine principles, the study seeks to identify and characterize potential genetic factors associated with VTE, ultimately providing valuable insights for clinical practice and future research in VTE genetics.