Genetic Analysis And Clinical Characterization Of Venous Thrombosis

Part One:Establishment of a genetic analysis panel based on next generation sequencing for patients with bleeding or thrombosis disorders[Objective]To develop an accurate and practical method for detection of genetic risk factors for patients with bleeding or thrombosis disorders,which can be used for early diagnosis and treatment guidance in Chinese thrombophilia patients.[Methods]Based on literatures,89 candidate genes related to bleeding or thrombosis disorders were selected to compose a gene panel.We enrolled 105 patients with venous thrombosis at the First Affiliated Hospital of Soochow University,Suzhou Municipal Hospital,and Suzhou Guangci Hospital.The clinical data and family history were collected.Gene variants of these patients were detected by next-generation sequencing and Ion S5 sequencing technique.[Results]Of the 105 patients with venous thrombosis,81 patients were found to have 85 different genetic variants.The detection rate was 77.1%.The association of genetic variants with laboratory hematological abnormalities was 62.9%(51/81).Among them,97.7%of patients had a heterozygous variant,2.3%had homozygous variants.Of the 81 patients detected with genetic variants,68 patients carried viriants of anticoagulant protein genes(SERPINC1,PROS1 and PROC),while 11 patients carried variants of other 9 genes(F2?F5?F8?PLG?THBD?FGG?FGB?HRG and PLAT).Among 85 variants,27 are that were not previously reported.17 of these new variants are considered pathogenic.[Conclusion]A genetic analysis panel was established to detect hereditary risk factors for bleeding and thrombosis diseases.Our analysis,although preliminary,indicate that the panel is a quick and accurate tool for genetic analysis of patients with venous thrombosis,which is valuable for clinicians to provide appropriate interventions for patients high risks to prevent the occurrence or recurrence of thrombosis.Part Two:Genetic and clinical characterization of a family with combined PROC and PROS1 genetic variants[Objective]To perform genetic analysis and clinical characterization of a family with combined heterozygous genetic variants of PROC and PROS1.[Methods]Peripheral blood was collected from all family members.Hematological phenotypes and activity of anticoagulant factors were analyzed.Target genes were amplified by PCR from DNA isolated from peripheral blood,and then analyzed by Sanger DNA sequencing and next-generation sequencing.[Results]4 members in the family displayed combined genetic variants in protein C and protein S,and six patients were accompanied with deep venous thrombosis(DVT).The influences of genetic and secondary factors on the incidence of DVT in the family members were analyzed.[Conclusion]DVT is a multifactorial disease.Pathogenic genetic variants of protein C and S are important genetic factor.However,patients with DVT are highly heterogeneous in their clinical phenotypes,suggesting a contribution of secondary factors to the DVT incidence.