Study Of Clinical And Molecular Pathogenesis In A Patient With Hereditary Protein S Deficiency

Objective:A patient with clinically diagnosed thrombophilia was analyzed for clinical manifestations,imaging,and laboratory tests.After this case was diagnosed as protein S deficiency(PSD),related gene sequencing was performed to search for genetic abnormalities that lead to the occurrence of hereditary protein S deficiency(HPSD),and to clarify its molecular pathogenesis and conduct genetic diagnosis..Methods:About this case with thrombophilia,clinical characteristics,imaging examination,and related laboratory examinations were analyzed.On the basis of excluding acquired thrombophilia,Anticoagulant proteins were measured.After clinical diagnosis of PSD,genes related to common hereditary thrombotic and hemorrhagic diseases were sequenced by next-generation sequencing to search for related gene mutations.Routine genetic sequencing was used to verify the discovered genetic abnormalitis and analyze its pathogenic mechanism.Results:Patients' protein S(protein S,PS)activity,free PS antigen,and total PS antigen were severely reduced in parallel.the patient's protein C activity,antithrombin activity,platelet count,platelet aggregation function,coagulation index,various coagulation factor activities,and autoantibodies series were all normal.So this patient is clinically diagnosed as PSD.The results of next-generation and routine sequencing suggest that there is a mutation in the c.1259T>A(p.L420X)heterozygosity in the PROS1 gene.This mutation causes premature termination of the amino acid code and affects the anticoagulation function of protein S.Conclusions:Based on the clinical features of one case with thrombophilia and related imaging and laboratory examinations,this patient can be diagnosed clinically PSD.At last,this case is diagnosed as HPSD by the results from gene sequencing.It was confirmed that the heterozygous mutation c.1259T>A(p.L420X)in the PROS1 gene is the molecular pathogenesis of the patient with HPSD.This gene mutation is first reported.