A genetic risk factor for thrombophilia in a Han Chinese family

Sun,Guoping; Jia,Yicong; Meng,Jingye; Ou,Minglin; Zhu,Peng; Cong,Shan; Luo,Yadan; Sui,Weiguo; Dai,Yong

doi:10.3892/mmr.2017.6217

A genetic risk factor for thrombophilia in a Han Chinese family

Authors:
- Guoping Sun
- Yicong Jia
- Jingye Meng
- Minglin Ou
- Peng Zhu
- Shan Cong
- Yadan Luo
- Weiguo Sui
- Yong Dai
View Affiliations

Affiliations: Central Laboratory, Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China, Department of Genetics, The Life Science College, Guangxi Normal University, Guilin, Guangxi 541002, P.R. China, Department of Hematology, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong 518020, P.R. China, Department of Nephrology, Guilin 181st Hospital, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China, Clinical Medical Research Center, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
Published online on: February 17, 2017 https://doi.org/10.3892/mmr.2017.6217
Pages: 1668-1672
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Thrombophilia is a multifactorial disorder involving environmental and genetic factors. Well‑known factors that result in predisposition to congenital disorders associated with thrombophilia include antithrombin deficiency, protein C and S deficiency, Factor V Leiden mutation, abnormal prothrombin and antiphospholipid syndrome. The present study revealed an association between a mutation of the F2 gene, which codes for coagulation factor II, thrombin, and the risk of thrombophilia in a Han Chinese family, of which four members (I‑2, II‑2, II‑3 and III‑1) had a history of deep venous thromboembolism. The disease was measured in this family using laboratory measurements and computed tomography angiography. To identify the abnormality underlying the increased thrombophilia risk, whole‑exome sequencing technology was used to analyze two affected individuals (II‑2 and III‑1). An exonic missense F2 mutation, T165M (NM_000506:c.C494T:p.T165M;rs5896), was identified from a total of 2,222 and 2,203 genetic variations observed in the two affected individuals, respectively, which were subsequently filtered and confirmed using Sanger sequencing. I‑2, II‑3 and III‑1 shared this mutation with the proband (II‑2), and II‑6 had a heterozygous form of the mutation. This deleterious mutation was not identified in normal controls. The present study may improve understanding of the function of the F2 gene.

View Figures

View References

1	Raffini L and Thornburg C: Testing children for inherited thrombophilia: More questions than answers. Br J Haematol. 147:277–288. 2009. View Article : Google Scholar : PubMed/NCBI
2	Kvasnička T, Hájková J, Bobčíková P, Cverhová V, Malíková I, Ulrych J, Bříza J, Dušková D, Poletínová S, Kieferová V and Kvasnička J: The frequencies of six important thrombophilic mutations in a population of the Czech Republic. Physiol Res. 63:245–253. 2014.PubMed/NCBI
3	Coriu L, Ungureanu R, Talmaci R, Uscatescu V, Cirstoiu M, Coriu D and Copaciu E: Hereditary Thrombophilia and thrombotic events in pregnancy: Single-center experience. J Med Life. 7:567–571. 2014.PubMed/NCBI
4	Spiezia L, Campello E, Bon M, Tison T, Milan M, Simioni P and Prandoni P: ABO blood groups and the risk of venous thrombosis in patients with inherited thrombophilia. Blood Transfus. 11:250–253. 2013.PubMed/NCBI
5	Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RT and Hamerton JL: Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively. Somat Cell Mol Genet. 13:285–292. 1987. View Article : Google Scholar : PubMed/NCBI
6	Walldorf U, Hovemann B and Bautz EK: F1 and F2: Two similar genes regulated differently during development of Drosophila melanogaster. Proc Natl Acad Sci USA. 82:5795–5799. 1985. View Article : Google Scholar : PubMed/NCBI
7	Al-Allawi NA, Badi AI, Goran MA, Nerweyi FF, Ballo HM and Al-Mzury NT: The contributions of thrombophilic mutations to genetic susceptibility to deep venous thrombosis in iraqi patients. Genet Test Mol Biomarkers. 19:500–504. 2015. View Article : Google Scholar : PubMed/NCBI
8	Simsek E, Yesilyurt A, Pinarli F, Eyerci N and Ulus AT: Combined genetic mutations have remarkable effect on deep venous thrombosis and/or pulmonary embolism occurence. Gene. 536:171–176. 2014. View Article : Google Scholar : PubMed/NCBI
9	Cosmi B, Legnani C, Pengo V, Ghirarduzzi A, Testa S, Poli D, Prisco D, Tripodi A and Palareti G: PROLONG Investigators (on behalf of FCSA Italian Federation of Anticoagulation Clinics): The influence of factor V Leiden and G20210A prothrombin mutation on the presence of residual vein obstruction after idiopathic deep-vein thrombosis of the lower limbs. Thromb Haemost. 109:510–516. 2013. View Article : Google Scholar : PubMed/NCBI
10	Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP and Rosendaal FR: Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA. 293:2352–2361. 2005. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Dai Y, Liu Y and Ren J: Mandibulofacial dysostosis, microtia, and limb anomalies in a newborn: A new form of acrofacial dysostosis syndrome? Clin Genet. 78:570–574. 2010. View Article : Google Scholar : PubMed/NCBI
12	Chen R, Im H and Snyder M: Whole-exome enrichment with the roche nimbleGen SeqCap EZ exome library SR platform. Cold Spring Harb Protoc. 2015:634–641. 2015. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Clark MJ, Chen R, Lam HY, Karczewski KJ, Chen R, Euskirchen G, Butte AJ and Snyder M: Performance comparison of exome DNA sequencing technologies. Nat Biotechnol. 29:908–914. 2011. View Article : Google Scholar : PubMed/NCBI
15	Ng PC and Henikoff S: SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 31:3812–3814. 2003. View Article : Google Scholar : PubMed/NCBI
16	Adzhubei I, Jordan DM and Sunyaev SR: Predicting functional effect of human missense mutations using polyPhen-2. Curr Protoc Hum Genet Chapter. 7:Unit7.202013.
17	Ge XH, Zhu F, Wang BL, Wang CM, Zhu B, Guan S, Ci HB, Sai LM, Jiang XK and Ren H: Association between prothrombin gene polymorphisms and hereditary thrombophilia in Xinjiang Kazakhs population. Blood Coagul Fibrinolysis. 25:114–118. 2014. View Article : Google Scholar : PubMed/NCBI
18	Iwahana H, Yoshimoto K and Itakura M: Highly polymorphic region of the human prothrombin (F2) gene. Hum Genet. 89:123–124. 1992. View Article : Google Scholar : PubMed/NCBI
19	Poort SR, Rosendaal FR, Reitsma PH and Bertina RM: A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 88:3698–3703. 1996.PubMed/NCBI