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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.
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Objective:To investigate the clinical characters and prognosis of patients with systemic-onset juvenile idiopathic arthritis associated interstitial lung disease (SoJIA-ILD).Methods:Clinical manifestations, imaging features and prognosis were analyzed in 75 patients with SoJIA between October 2010 and December 2019 in the Second Affiliated Hospital of Wenzhou Medical University.Results:Seventy-five patients with SoJIA were enrolled. Among 12 children with SoJIA-ILD, 6 were male and 6 were female. The mean age of onset was (7.9±2.6) years. All of the 12 patients had fever. Ten patients had arthritis which mainly occurred in large joints. The incidence of arthritis was knee, hip and shoulder from high to low. Two patients had no joint involvement at the onset of the disease and had no joint symptoms during the follow-up. Nine patients (75%) had fever, rash and arthritis at the same time. The clinical features of ILD were mostly nonspecific, including cough in 8 cases (75%), shortness of breath in 7 cases (58%), chest pain in 3 cases (25%), velcro sound in 4 cases (33%) and pulmonary hypertension in 1 case (8%). Inflammatory indicators were all signifi-cantly elevated, among which was CRP (235±112) mg/L, ESR (39±25) mm/1 h, serum ferritin (SF) (1 312±384) ng/ml and serum amyloid A (SAA) (212±101) mg/L. High resolution computed tomography (HRCT) of the chest presented as reticular or line shadows in 12 patients, consolidation in 7 patients, ground interlobular septal thickening in 5 patients, glass opacity in 4 patients and honeycomb lung in 1 patient. ILD occurred in 4 cases (33%) in the early stage of SoJIA (disease course ≤6 months), and 8 cases (67%) in the medium and late stages of the disease course (>6 months), but all appeared in the active status of SoJIA. All of 12 patients received glucocorticoids therapy, 11 patients received high dose of glucocorticoid (>1 mg·kg -1·d -1) and 2 pa-tients received intravenous methylprednisolone pulse therapy. All of 12 patients were treated with glucocorti-coids combined with immunosuppressant or disease modifying antirheumatic drugs and 5 patients needed dual therapy or triple therapy. One case had been treated with biological agents before the occurrence of lung injury and the other 11 cases had not used biological agents before. After the diagnosis of SoJIA complicated with ILD, 4 cases were treated with tocilizumab. Macrophage activation syndrome (MAS) was found in 7 cases and 25% had MAS for two times or more. Ten patients had partial remission or complete remission and 2 patients died of respiratory failure. Conclusion:SoJIA-ILD maybe asymptomatic at the early stage of the disease. It is associated with disease activity of SoJIA. HRCT examination is very important for early diagnosis. Patients with SoJIA-ILD have higher rate of recurrence, death and MAS. It needs to arouse the clinicians' attention.
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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.
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Objective To assess the value of acoustic radiation force impulse (ARFI) imaging in the pathological damage of Henoch-Schonlein purpura nephritis on children by comparison with renal biopsy.Methods 50 cases of healthy control group as group A; 58 children with HSPN were divided into three groups according to pathological grading:Ⅰ ～ Ⅱ class (group B),Ⅲ class (group C) and Ⅳ ～ Ⅵ class (group D).ARFI was then used to measure the shear wave velocities(SWV) of renal cortex of each group,compared the differences SWV of each group.Results SWV values of children's renal cortex with HSPN were significantly higher (t =5.883,P =0.017) than those in the group A.Pairwise comparisons found that there were statistically significant differences between group D and the other three groups (P ＜0.05).According the ROC curve,the cut-off value of SWV was 2.59 m/s when the maximum area under the curve equal to 0.719,the sensitivity and specificity were 63％ and 67％.Conclusions ARFI technology can quantify the elastic properties of the kidney,which is expected as an important indicator to evaluate the pathological extent of damage of the HSPN.