Abstract:

Objective To analyze and perform genetic testing for a case of pregnancy with antithrombin deficiency. Methods The clinical data were collected，and plasma antithrombin activity(AT：A)，prothrombin time(PT)，activated partial thromboplastin time(APTT)，thrombin time(TT)，fibrinogen(Fib)，D-dimer(DD)，fibrinogen degradation product(FDP)，protein C activity(PC：A) and protein S activity(PS：A)were determined. The proband genes(PROC，PROS1，SERPINC1，SERPIND1，PLG，PROCR，THBD，ADAMTS13，HRG，TFPI，CPB2，HABP2，PLAT，PLAU，SERPINA10，SERPINE1，SERPINF2，CALR，GP6，JAK2，MPL)，coagulation factor related gene at the transcription start point，5'-untranslated region(UTR)，coding region，splicing point 8 bp intron sequence region，transcription terminator point mutation，small deletion or duplication and splicing site were determined for the presence of mutations. Sanger sequencing was used to validate the mutation sites. Bioinformatics analysis of the mutation sites was performed to clarify pathogenicity. Results The patient had decreased AT：A. The patient had a c.380G>A(p.Cys127Tyr)heterozygous mutation in exon 2 of the SERPINC1 gene，a c.1324G>C(p.Glu442Gln) heterozygous mutation in exon 10 of the JAK2 gene，and a c.389T>G(p.Leu130Trp)heterozygous mutation in exon 2 of the SERPINA10 gene. The c.380G>A(p.Cys127Tyr) mutation in the SERPINC1 gene was not included in the public SNP databases for normal populations(ExAC database，1000G dbSNP13 database and gnomAD)，and no relevant reports of this site were seen in the ClinVar database，OMIM database and HGMD database. PolyPhen-2，MutationTaster and CADD online software predicted it as a pathogenic mutation. The c.1324G>C(p.Glu442Gln) mutation in the JAK2 gene and the c.389T>G(p.Leu130Trp) mutation in the SERPINA10 gene were both classified as mutations of uncertain significance. Sanger sequencing results showed the presence of all 3 mutations. Structural analysis of protein mimicry showed that the c.380G>A(p.Cys127Tyr) mutation in the SERPINC1 gene can lead to structural changes in the protein，thereby affecting protein function. Conclusions The c.380G>A(p.Cys127Tyr)mutation in the SERPINC1 gene may lead to hereditary AT deficiency. The monitoring of coagulation-related indicators and timely molecular diagnosis can help improve pregnancy outcomes in patients with hereditary AT.

Key words: SERPINC1 gene, Thrombosis, Heredity antithrombin deficiency, Pregnancy