Compound heterozygous mutation of MUSK causing fetal akinesia deformation sequence syndrome: A case report

BACKGROUND Fetal akinesia deformation sequence(FADS)is a broad spectrum disorder with absent fetal movements as the unifying feature.The etiology of FADS is heterogeneous and mostly still unknown.A prenatal diagnosis of FADS relies on clinical features obtained by ultrasound and fetal muscle pathology.However,the recent advances of next-generation sequencing(NGS)can effectively provide a definitive molecular diagnosis.CASE SUMMARY A fetus presented after 24 wk and 6 d of gestation with absent fetal movements and multiple abnormal ultrasonographic signs.The mother had had a previous abortion due to a similarly affected fetus a year before.A clinical diagnosis of FADS was made.The parents refused cord blood examination and chose abortion.A molecular diagnosis of fetal muscle using NGS of genes found a compound heterozygous mutation in the MUSK gene:c.220C>T(chr9:113449410 p.R74W)and c.421delC(chr9:113457745 p.P141fs).CONCLUSION To our knowledge,this is the first report in China showing that a mutation in MUSK is associated with FADS.This supports previous finding that a lethal mutation of MUSK will cause FADS.A precise molecular diagnosis for genetic counseling and options for a prenatal diagnosis of FADS are very important,especially for recurrent FADS;this may also provide evidence for both prenatal and preimplantation genetic diagnoses.

Postpartum Hemorrhage Following Cesarean Delivery in Women with a Scarred Uterus:A Retrospective Cohort Study

Objective:To develop a model to predict the risk of postpartum hemorrhage(PPH)following cesarean delivery in women with a scarred uterus.Methods:A total of 4,637 pregnant women with scarred uterus who underwent a cesarean delivery at a large hospital between January 2014 and December 2017 were enrolled.The women were divided into PPH(n=287)and non-PPH(n=4,350)groups.A model to predict PPH(blood loss≥1,000 mL within 24 h following cesarean delivery)was developed using multivariate logistic regression analysis.Receiver operating characteristic curve was drawn,and the area under curve(AUC)was calculated.Results:The incidence of PPH was 6.19%(287 of 4,637 women).Seven independent risk factors were associated with PPH:maternal age(odds ratio[OR]=1.42,95%confidence interval[CI]:1.02-1.97),previous gravidity(OR=1.24,95%CI:1.01-1.50),placental location(posterior wall of uterus,OR=0.69,95%CI:0.47-1.02;other locations,OR=1.21,95%CI:0.81-1.80),placenta previa(incomplete placenta previa,OR=10.51,95%CI:5.99-18.42;complete placenta previa,OR=31.65,95%CI:21.07-47.54),placenta accreta(OR=6.39,95%CI:4.02-10.16),hypertensive disorders of pregnancy(OR=2.27,95%CI:1.40-3.68),and fetal position(breech position,OR=2.07,95%CI:1.19-3.60;transverse position,OR=1.07,95%CI:0.48-2.41).A predictive model with AUC of 0.89 was developed(95%CI:0.86-0.91,P<0.001).Conclusions:A model was developed to predict PPH following cesarean delivery in women with a scarred uterus.

Lin28B Expression in Reduced Uterine Perfusion Pressure Rat Model

Objective:Preeclampsia(PE)is a serious complication of pregnancy.Placental ischemia could be an initiating event,but the molecular mechanisms underlying PE are unclear.Lin28B,a paralog of Lin28 RNA-binding protein,is predominantly expressed in human placenta,and decreased Lin28B expression may play a role in PE by reducing trophoblast invasion.The current study was intended to verify whether Lin28B plays a role in the pathogenesis of PE in rat model for reduced uterine perfusion pressure(RUPP).Methods:We used RUPP rat model.The changes in blood pressure,24-h urine protein excretion,and fetal development in RUPP rats were recorded and compared to those of normal pregnant(NP)rats.Furthermore,the expression of Lin28B mRNA and protein in placenta was determined using quantitative real-time polymerase chain reaction,Western blotting,and immunohistochemistry.Results:The blood pressure,24-h urine protein excretion,and embryo absorption rate were significantly increased in RUPP rats on the 20^(th) day of gestational period compared with the NP rats(P<0.001).However,there was no difference in the weight of placenta in RUPP versus NP rats(P>0.05).The expression levels of Lin28B mRNA and protein in the placenta of RUPP rats were also significantly decreased in comparison to NP rats(P<0.001).Conclusion:Our results show that the expression of Lin28B in the placenta of RUPP rats is different from that in NP rats,thus suggesting a role of Lin28B in the pathogenesis of preeclampsia.

Expression and clinical significance of calcitonin receptor stimulating peptide-3(CRSP-3) in placenta tissue of preeclampsia patients

Objective To study clinical significance and the difference of calcitonin receptor stimulating peptide-3 （CRSP-3） expression in placenta tissue between normal preg- nancies and patients with preeclampsia. Methods CRSP-3 expression position in placenta tissues of 50 cases with preeclampsia （preeclampsia group： 25 cases of mild preeclampsia and 25 cases of severe preeclampsia） and 30 cases of normal late pregnancy （control group） was detected using immunohistochemical methods. CRSP-3 mRNA and protein expression in placenta tissues was detected using Real-time PCR and Western blotting method. Results Syncytiotrophoblast and cytotrophoblast cells expressed CRSP-3 in placenta tissue of preeclampsia and normal pregnancy patients. The expression levels of CRSP- 3 mRNA and protein in placenta tissue ofpreeclampsia patients were higher than those in control group （P〈O.05）. The expression levels of CRSP-3 mRNA and protein in placenta tissue of severe preeclampsia patients were higher than those in control group （P〈0.01） significantly. The expression level of CRSP-3 mRNA and protein in placenta tissue of severe preeclampsia group was slightly higher than that in mild preeclampsia group, but there were no statistical differences between the two groups （P〉0. 05）. Conclusion The up-regulation of CRSP-3 in placenta of preeclamptic patients may be associated with the etiology of preeclampsia, but may have no relation with progress and degree of preeclampsia.