Molecular analysis of the genotypes and phenotypes in three pedigrees with inherited antithrombin defidency
10.3760/cma.j.issn.1009-9158.2009.11.013
- VernacularTitle:三个遗传性抗凝血酶缺陷症家系临床表型和基因型分析
- Author:
Yingting WU
;
Guanqun XU
;
Liwei ZHANG
;
Jing DAI
;
Qiulan DING
;
Xiaodong XI
;
Xuefeng WANG
;
Hongli WANG
- Publication Type:Journal Article
- Keywords:
Blood coagulation disorders;
inherited;
Pedigree;
Fibrin;
Mutation;
Genotype;
Thrombosis
- From:
Chinese Journal of Laboratory Medicine
2009;32(11):1257-1261
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical phenotype and genotype in three probands with antithmmbin(AT)deficiency and their families,and to identify the molecular mechanism of AT deficiency.Methods Chromogenic substrate method and immunoturbidimetry assay was used to detect the plasma levels of AT:A and AT:Ag,respectively.Genomic DNA was extracted from the peripheral blood.All 7 exons and the flanking sequences were amplified by PCR.and the abnormal mutant genes were analyzed by direct sequencing.Western blot was used to detect the AT levels and thrombin generation tests were used to detect coagulation status.Results The plasma levels of AT:A and AT:Ag of the three probands declined by 50%.G7386C(Trp225Cys)mutation in exon 4,C2591G(Ser36stop)in exon 2 and C9819T(Arg359stop)in exon 5 were characterized in the three prebands and they could result in W(Trp)225C(Cys)missense mutation,S(Set)36X(stop)nonsense mutation and R(Arg)359X(stop)nonsense mutation respectively,The testing results of phenotype and genotype from some of their family members showed consistent with results from the probands.Western blot results indicated that the Icyels of PC:Ag were lower compared with the normal pooled plasma.The hypercoagulative status was present in the probands using thrombin generation tests.Conclusions Type Ⅰ hereditary AT deficiency was found in these three families.The 3 heterozygous mutations.W225C,S36X and R359X are genetic defects of hereditary AT deficiency.W225C and S36X have not been described before.
