Analysis of clinical phenotype and genetic mutations of a pedigree of familial hemophagocytic lymphohistiocytosis

Objective To investigate the expression of placenta-derived RASSF1A gene in maternal plasma during first and second trimesters,and to explore its value for the prediction of pre-eclampsia.Methods For 325 pregnant women of the first trimester,free DNA of plasma samples was extracted at 7-12,13-18,and 19-24 gestational weeks,respectively.Methylation-sensitive restriction enzyme digestion followed by fluorescence quantitative PCR (MSRE+PCR) was employed for analyzing the concentrations of hypermethylatedRASSF1A gene.Blood pressure,proteinuria and clinical feature were monitored at the same time.Those who had subsequently developed pre-eclampsia were selected as the pre-eclamptic group,30 normal pregnant women were selected as the control group.Hypermethylated RASSF1A gene in maternal plasma was retrospectively analyzed.The relationship between clinical classification,type of pre-eclampsia and concentrations of the gene were further analyzed.Results Twenty-six out of the 325 pregnant women developed pre-eclampsia as their only complication.At 13-18 gestational weeks,the mean concentrations of fetus-specific RASSF1A sequences were 141.62 copies/mL in maternal plasma of pre-eclamptic pregnancies,which was significantly greater than that of the controls (98.90 copies/mL).Fetus-derived RASSF1A levels were 2.03 fold higher in pre-eclamptic subjects than controls at 19-24 gestational weeks.There was a significant difference in the level of hypermethylated RASSF1A gene between the mild and severe pre-eclamptic subjects at 13-24 gestational weeks (P＜0.05).The concentrations of the sequences were significantly higher in early-onset severe pre-eclampsia than late-onset severe pre-eclampsia at 19-24gestational weeks (P＜0.05).Conclusion Altered expression of hypermethylated RASSF1A gene may be detected in maternal plasma during second trimester,which has important significance for early prediction of pre-eclampsia. Key words: Pre-eclampsia;  Hypermethylated RASSF1A ;  Fluorescence quantitative PCR;  Noninvasive prenatal diagnosis