Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the molecular basis of type I protein S (PS) deficiency in two unrelated Japanese families, in which both probands developed pulmonary embolism associated with deep vein thrombosis. Nucleotide sequencing of amplified DNA revealed distinct point mutations in the PROS1 gene of the probands, which were designated protein S Sapporo 1 and protein S Sapporo 2. Additional mutations in the PROS1 gene were excluded by DNA sequencing of all exons and intron/exon boundaries. In the 25-year-old Japanese male patient who carried protein S Sapporo 1, we identified a heterozygous A-to-T change in the invariant ag dinucleotide of the acceptor splice site of intron f of the PROS1 gene. This mutation is a novel splice site mutation that impairs normal mRNA splicing, leading to exon 7 skipping, which was confirmed by platelet mRNA analysis. Translation of this mutant transcript would result in a truncated protein that lacks the entire epidermal growth factor-like domain 3 of the PS molecule. In a 31-year-old Japanese male and his younger brother who each carried protein S Sapporo 2, we detected a previously described heterozygous T-to-C transition at nucleotide position 1147 in exon 10 of the PROS1 gene, which predicts an amino acid substitution of tryptophan by arginine at residue 342 in the laminin G1 domain of the PS molecule. Both mutations would cause misfolding of the PS protein, resulting in the impairment of secretion, which is consistent with the type I PS deficiency phenotype.
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PMID:One novel and one recurrent mutation in the PROS1 gene cause type I protein S deficiency in patients with pulmonary embolism associated with deep vein thrombosis. 1686 38

Thrombophilia refers to a group of conditions where the blood clots more easily than normal. These blood clots can cause problems such as deep vein thrombosis or pulmonary embolism. Most kinds of mutated coagulation factors II (F2) exhibit lower procoagulant activity, but in some cases, a higher coagulation rate has been observed. The underlying mechanism is that those variations can prevent F2s from being inhibited by antithrombin, leading to a contiguous activation of procoagulation, and causing recurrent thromboembolism. In this study, a patient was admitted to our hospital due to repeated chest pain for 2 days and aggravated for 4 h. A medical history investigation showed that he had three deep venous thromboses in the lower limbs and one portal vein thrombosis events during the past 10 years. The electrocardiogram showed Q wave elevation and slight ST segment elevation in lead V2, and coronary angiogram showed a total occlusion of the left anterior descending artery. Laboratory testing found that troponin I was obviously elevated. Family history also indicated that both his father (II-3) and grandfather (I-1) died from pulmonary thromboembolism. Whole-exome sequencing was performed to detect the genetic lesion of the patient, and a novel mutation (c.1621 C>T/p.R541W) of F2 was identified in the patient. This novel mutation resulted in a substitution of arginine by tryptophan, leading to antithrombin resistance (ATR). Our study is consistent with previously published papers. In conclusion, this study not only identifies a novel mutation of F2 and will contribute to the genetic diagnosis and counseling of families with thrombosis but also suggests that the site p.R541 of F2 may play a crucial role in thrombosis.
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PMID:A Novel Heterozygous Variant in F2 Gene in a Chinese Patient With Coronary Thrombosis and Acute Myocardial Infarction Leads to Antithrombin Resistance. 3219 38