Pedigree analysis of a child with neonatal diabetes / 临床儿科杂志

10.3969/j.issn.1000-3606.2013.06.019

Analysis of causes and risk factors of postpartum hemorrhage in hepatitis B virus-infected parturients / 中华传染病杂志

Objective To investigate the causes and risk factors of postpartum hemorrhage (PPH) in hepatitis B virus (HBV) infected parturient.Methods Retrospective analysis was performed on the 1021 HBV infected parturient from Shanghai Public Health Clinical Center from July 2005 to June 2011.The comparisons were done by chi-square test.Results Among 1021 cases of HBV infected parturient,868 (85.01％) were asymptomatic and the PPH rate was 2.76％ (24/868) ;the remaining 153 cases (14.99％) were chronic active hepatitis B and the PPH rate was 16.99％(26/153).The difference between two groups was statistically significant (x2 =56.541,P＜0.01).The total incidence rate of PPH was 4.89％ (50/1021) and 17 cases (34.00％) were postpartum hemorrhage＞1000mL.The causes of PPH included uterine inertia (30/50,60.00％),abnormal placenta (11/50,22.00％),dysfunction of coagulation (5/50,10.00％) and lesion of birth canal (4/50,8.00％).The risk factors of PPH included delivery mode (x2 =6.528,P=0.038),abortion times (x2 =16.269,P=0.000),delivery times (x2 =6.990,P=0.008),ALT levels (x2=56.541,P=0.000) and HBV DNA (x2 =64.706,P=0.000).Conclusions The main causes of PPH in HBV infected parturient include uterine inertia,abnormal placenta,lesion of birth canal and dysfunction of blood coagulation.PPH is correlated with abortion times,delivery times,delivery mode,liver function and HBV DNA.The incidence of PPH in parturient with chronic active hepatitis B is higher than asymptomatic parturient.

Study of molecular mechanisms of hereditary protein C deficiency in four Chinese families / 中华检验医学杂志

Objective To investigate the phenotype, genotype and molecular mechanisms in four Chinese pedigrees with venous thrombosis caused by hereditary PC deficiency. Methods The plasma activity of PC: A, TPS: A and FPS: A of the probands and their family members were detected with chromogenic and coagulation assay. The antigen of PC and FPS were identified with ELISA. Thrombin generation tests were applied to indicate the coagulation status. All of the nine exons and intron-exon boundaries of PC gene and PS gene were amplified by PCR and directly sequenced for mutaiton investigation. Results Compound heterozygous mutations of L-34P, K150del and A209V with 36% of PC: A and 57% of PC: Ag were identified in proband 1. PC: A was 46% , PC: Ag was 64. 4% while TPS: A, FPS: A and FPS: Ag were 36% , 19.5% and 20.9% respectively in proband 2. Two independent heterozygous mutations of R147W in PC gene inherited from his mother and T519stop in PS gene inherited from his father were identified. The anticoagulant activity of Proband 2 and his parents were declined in thrombin generation assay. In proband with PS defeciency and his father, the inhibition of thrombin generation capacity was decreased with exogenous APC, while his mother did not have significant difference. In Proband 3, PC: A was 32% while PC: Ag was 48.42% . Two independent mutations of R147W and R178W in Exon 7 were detected. Compound heterozygous mutations of R178W and D255H,with 21% of PC : A and 18. 36% of PC: Ag were identified in the Proband 4. Conclusions Hereditary PC deficiency or combined PC and PS deficiency result in venous thrombosis in four Chinese families. Mutants of L-34P, A209V, R178W, R147W and D255H might be the molecular mechanisms of PC deficiency.

Molecular analysis of the genotypes and phenotypes in three pedigrees with inherited antithrombin defidency / 中华检验医学杂志

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.