RÉSUMÉ
Objective:To analyze the indications for invasive prenatal diagnosis in the third trimester and summarize the pregnant outcome.Methods:Clinical data of 121 women who underwent invasive prenatal diagnosis in the third trimester in the prenatal diagnostic center of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 was retrospectively analyzed. Different genetic diagnostic methods were used according to different indications. Indications and results of prenatal diagnosis, as well as the complications within two weeks after the invasive procedure, pregnancy outcome, and neonatal follow-up of all the participants were described.Results:Among the 121 cases, 107 cases underwent amniocentesis, seven underwent percutaneous umbilical blood sampling, and seven had both procedures performed at the same time (one underwent thoracocentesis at the same time). Newly identified ultrasound abnormalities in the second and third trimesters were the main indications for prenatal diagnosis, accounting for 99.2%(120/121), of which short limbs and fetal growth restriction accounted for 25.0% (30/120) and 20.0% (24/120), respectively. Genetic abnormalities and congenital diseases were detected in 20 cases with a detection rate of 16.5%(20/121). Among them, there were nine cases of achondroplasia, five cases of pathogenic copy number variations, one case of achondroplasia with pathogenic copy number variation, one trisomy 18, one 47,XXX, one tetrasome mosaicism of 12p, one de novo WTX c. 1072(Exon2) C>Tp.R358X heterozygous mutation, and one fetal hypoproteinemia. In addition, six cases with copy number variation of unknown significance (VUS) were detected, noting for a detection rate of 5.0%(6/121). Among the 20 cases with abnormal detection, 15 were terminated, two delivered prematurely before obtaining the prenatal diagnosis results, one underwent cesarean section before obtaining prenatal diagnostic results and two continued the pregnancies. In the six cases with VUS, one was terminated and the other five continued the pregnancy. Only one case had preterm premature rupture of membranes 2 d after amniocentesis and the incidence rate of complications after all kinds of invasive procedures was 0.8% (1/121). During the neonatal follow-up, postnatal whole exome sequencing revealed monogenetic disorder in two cases with normal prenatal diagnostic results; the patient with 12p chimerism had developmental delay; the one with WTX mutation deceased on the day of born; the rest newborns developed normally. Conclusions:As a relatively safe method, invasive prenatal diagnosis in the third trimester is of great importance and value in reducing the miss diagnostic rate of fetuses with severe genetic diseases and birth defects. The appropriate application of prenatal whole exome sequencing could further help to decrease the miss diagnostic rate of monogenetic disorder.
RÉSUMÉ
Objective To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.
RÉSUMÉ
Objective To reduce the screening positive rate (SPR) and improve clinical efficiency of maternal serum screening for Down's syndrome.Methods Nine thousand and thirty-three cases of second trimester maternal serum screening for Down's syndrome were included from Apr.2013 to Apr.2014 in the present study.The screening results,all basic data and equation curves were analyzed retrospectively.Based on the data from the authors' laboratory,the important adjustment parameters were simulated.Combined with postnatal follow-up results,the quality and clinical performance of second trimester serum screening for Down's syndrome were evaluated.Results The SPR of second trimester serum screening for Down's syndrome was 6.69％(604/9033),the detection rate (DR) was 75％(3/4),and FPR was 6.65％(601/9033).The median multiple of median (MOM) of alpha-fetoprotein (AFP) was low and SPR was high,and MOM of free human chorionic gonadotropin β subunit (free hCGβ) were high and SPR was high,while MOM of unconjugated estriol (uE3) were a little bit low,and SPR was slightly high.Considering these three factors,it is believed that the screening positive rate is high.By the simulation adjustments of MOM value equations (AFP and free hCGβ) and weight correction equation,the SPR reduced to 4.11％(371/9033) after recalculating the risk,FPR declined to 4.07％(368/9033),and no more Down's syndrome fetus were missed compared with postnatal follow-up results.Conclusion Based on a localized setting depending on the local laboratory data,we suggest that the MOM value distributions(AFP,free hCGβ and uE3) and maternal weight should be regularly adjusted since it is a useful way to reduce the false-positive rate and improve clinical efficiency of maternal serum screening for Down's syndrome.