一个遗传性纤溶酶原缺陷症家系的表型与基因突变分析

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Abstract Objective: To detect the phenotype and gene mutation of a family with hereditary plasminogen (PLG) deficiency and to investigate the molecular mechanism of its pathogenesis. Methods: Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (DD), fibrinogen degradation product (FDP), plasminogen activity (PLG:A), plasminogen antigen (PLG:Ag), antithrombin activity (AT:A), protein C activity (PC:A) and protein S activity (PS:A) were tested in the diagnosis of the proband and his family members (3 generations and 4 persons). Direct DNA sequencing was used to analyze all exons and exon-intron boundaries of the PLG gene, as well as the 5’ and 3’ non-translation regions and the corresponding mutation site regions of family members, confirmed by reverse sequencing. ClustalX-2.1-win software was used to analyze the conserved amino acid sequence of homologous species. PolyPhen-2, PROVEAN, SIFT and Mutation Taster were used to forecast the possible impact of mutant amino acids on protein function. Finally, the protein model and amino acid interaction analysis was performed on the mutation sites using Swiss-Pdb Viewer software. Results: The PLG:A of the proband and his grandfather and father were reduced to the half, while the PLG:Ag was normal, the results being 45%, 95%; 64%, 94% and 64%, 104% respectively. Gene sequencing revealed that the PLG gene of the proband had c.1858G>A heterozygous missense in exon 15, resulting in p.Ala601Thr. Its grandfather and father had the same genetic mutation. Ala601 was highly conserved among its 11 homologous species. The four online bioinformatics software have consistent predictions, all of which were harmful mutations that affect the PLG function, leading to the corresponding diseases. Conclusion: The proband’s PLG gene exon 15 has heterozygous missense mutation of c.1858G>A(p.Ala601Thr) . And the three generations of the grandparents are Ala601Thr heterozygotes, with the mutation in accordance with Mendelian inheritance law and with the family plasminogen activity reduced.

Key words： hereditary plasminogen deficiency gene mutation heterozygosis model analysis

Received: 24 February 2019

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	XIA Hong
	ZHANG Haiyue
	LIU Meina
	LI Xiaolong
	YANG Lihong
	WANG Mingshan.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2019/V49/I6/432

[1] SCHUSTER V, HÜGLE B, TEFS K. Plasminogen deficien-cy[J]. J Thromb Haemost, 2007, 5(12): 2315-2322.
[2] MEHTA R, SHAPIRO A D. Plasminogen deficiency[J]. Haemophilia, 2008, 14(6): 1261-1268.
[3] 程晓丽, 杨丽红, 黄国咏, 等. 纤溶酶原Ala601Thr突变导致的遗传性异常纤溶酶原血症表型与基因型分析[J]. 中华检验医学杂志, 2016, 39(5): 366-371.
[4] KIDA M, WAKABAYASHI S, ICHINOSE A. Expression and induction by IL-6 of the normal and variant genes for human plasminogen[J]. Biochem Biophys Res Commun, 1997, 230(1): 129-132.
[5] AOKI N, MOROI M, SAKATA Y, et al. Abnormal plasminogen. A hereditary molecular abnormality found in a patient with recurrent thrombosis[J]. J Clin Invest, 1978, 61(5): 1186-1195.
[6] LOTTENBERG R, DOLLY F R, KITCHENS C S. Recurring thromboembolic disease and pulmonary hypertension associated with severe hypoplasminogenemia[J]. Am J Hematol, 1985, 19(2): 181-193.
[7] KAZAMA M, TAHARA C, SUZUKI Z, et al. Abnormal plasminogen, a case of recurrent thrombosis[J]. Thromb Res, 1981, 21(4-5): 517-522.
[8] GIROLAMI A, MARAFIOTI F, RUBERTELLI M, et al. Congenital heterozygous plasminogen deficiency associated with a severe thrombotic tendency[J]. Acta Haematol, 1986, 75(1): 54-57.
[9] LEEBEEK F W, KNOT E A, TEN CATE J W, et al. Severe thrombotic tendency associated with a type I plasminogen deficiency[J]. Am J Hematol, 1989, 30(1): 32-35.
[10] SARTORI M T, PATRASSI G M, THEODORIDIS P, et al. Heterozygous type I plasminogen deficiency is associated with an increased risk for thrombosis: a statistical analysis in 20 kindreds[J]. Blood Coagul Fibrinolysis, 1994, 5(6): 889-893.
[11] PAPAGEORGHIOU A T, YU C K, NICOLAIDES K H. The role of uterine artery Doppler in predicting adverse pregnancy outcome[J]. Best Pract Res Clin Obstet Gynaecol, 2004, 18(3): 383-396.
[12] LYALL F. Priming and remodelling of human placental bed spiral arteries during pregnancy-a review[J]. Placenta, 2005, 26(Suppl A): 31-36.
[13] 李绅, 王美, 耿顺玲, 等. 早孕前、后子宫动脉血流与妊娠结局的相关性研究[J]. 中华临床医师杂志(电子版), 2015, 9(2): 218-222.
[14] MIYATA T, IWANAGA S, SAKATA Y, et al. Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site[J]. Proc Natl Acad Sci U S A, 1982, 79(20): 6132-6136.