Recurrent deep vein thrombosis caused by heterozygous missense mutation of the protein S gene: genetic analysis of a case / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the molecular pathogenesis of protein S deficiency in an adolescent case of recurrent deep vein thrombosis (DVT).</p><p><b>METHODS</b>Blood samples from the patient and his family members were collected for detection of the coagulation parameters by one-step clotting method, and the protein S (PS) and protein C activities were measured by a chromogenic assay. Enzyme-linked immunosorbent assay was employed for detecting the levels of free PS antigen. All the exons and exon-intron boundaries of the patients PS gene were amplified using PCR and analyzed by direct sequencing.</p><p><b>RESULTS</b>As carriers of hereditary PS deficiency, both the patient and his father showed a heterozygous C82792T point mutation in the 10th exon of their PS gene which resulted in the substitution of arginine314 by cysteine in the polypeptide chain of PS protein.</p><p><b>CONCLUSION</b>Recurrence of DVT in this patient is the result of hereditary PS deficiency caused by a novel heterozygous missense mutation in the PS gene.</p>

Two novel mutations in one pedigree with hereditary Factor VII deficiency / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the mutations of coagulation factor VII (FVII) gene in one pedigree with hereditary FVII deficiency, and to investigate the molecular mechanisms of FVII deficiency.</p><p><b>METHODS</b>FVII gene mutations were analysed in the pedigree by direct DNA sequencing. The mutated DNA fragments were cloned into pMD19-T simple TA vector, and sequenced to confirm their distribution on chromosome. The plasma activity of FVII of the probands and their family members was detected with coagulation assay. The antigen of FVII were identified with ELISA.</p><p><b>RESULTS</b>Three gene mutations were detected in the pedigree: A/G to C at 15386 resulting in Arg353Pro/Gln353Pro, A to T at 15274 resulting in Lys316Stop, all three mutations were heterozygotes. Three kinds of polymorphisms were identified in his father: A to G transition at position 15386 resulting in Arg353Gln, heterozygotic deletion of 2050 - 2059 cctatatcct in promoter and G to A mutation in intron 1a, the same polymorphisms were found in his grandfather. The three polymorphisms were located in the same chromosome of his father.</p><p><b>CONCLUSION</b>Two mutations were found in the pedigree with hereditary FVII deficiency. One is nonsense mutation (Lys316Stop), the other is missense one (Gln353Pro). Gln353Pro and Lys316Stop might be the molecular mechanisms of FVII deficiency. The two novel mutations were reported for the first time in the literature.</p>