Objective:To investigate the performance of chromosome karyotype, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in prenatal diagnosis of true fetal chromosome mosaicism. Methods:This retrospective study enrolled 40 women with true fetal chromosome mosaicism from 4 071 singleton pregnant women who were indicated for and underwent amniocentesis or/and cordocentesis in the the First Affiliated Hospital of Sun Yat-sen University from April 2018 to August 2021. The results of chromosome karyotyping, CMA and FISH, the types of chromosomal mosaicism, mosaicism ratio and pregnancy outcomes were analyzed using Chi-square test. Results:(1) The detection rate of true fetal mosaicism was 0.98% (40/4 071). (2) Sex chromosome mosaicism accounted for 42.5% (17/40). Other chromosomal mosaicism involved chromosomes 21, 22, 18, 16, 7, 12, 15, 17 and 20, as well as balanced chromosomal translocation. (3) The detection rate of true fetal mosaicism by chromosome karyotyping was 77.4% (24/31) from amniotic fluid samples and 10/19 from umbilical cord blood samples, while that data by CMA was 76.7% (23/30) and 7/11,respectively. (4) Of the 40 pregnant women with fetal chromosome mosaicism, FISH test was performed on 20 cases (14 cases were verified with both amniotic fluid and umbilical cord blood samples, five with amniotic fluid samples and one with umbilical cord blood sample), and all of the diagnosis of mosaicism were confirmed. For those with mosaicism ratio <30%, the detection rate by FISH was higher than that by CMA among amniotic fluid samples [14/19 vs 43.5% (10/23), χ2=3.88, P=0.049]. (5) Among the 40 pregnant women, five were lost to follow-up; 18 chose to terminate the pregnancy; and 17 continued the pregnancy to delivery. No abnormalities in mental or physical development were reported in the 17 neonates after birth or during on-line follow-up between 6 to 24 months old. Of the 14 pregnant women with mosaicism ratio <30% which confirmed by FISH, eight chose to continue the pregnancy, and no abnormalities in mental development or growth were found in the neonates. Conclusions:In prenatal diagnosis of true fetal choromosome mosaicism, the incidence of sex chromosome mosaicism is the highest. FISH may improve the prenatal diagnosis rate of mosaicism and is more accurate in determining the mosaicism ratio. The combination of FISH, CMA and chromosome karyotyping would significantly improve the detection rate of chromosomal mosaicism and assess the mosaicism ratio more accurately, which is of great value in clinical consultation and evaluation of fetal prognosis.

Objective:To investigate the prenatal genetic features and the factors influencing the prognosis of twin reversed arterial perfusion sequence (TRAPS) in monochorionic twin pregnancies.Methods:A total of 99 cases diagnosed with TRAPS by prenatal ultrasound in the First Affiliated Hospital of Sun Yat-sen University from July 1, 2007, to December 31, 2021, were included retrospectively. The prenatal genetic features of acardiac and pump twins were analyzed. Eighty-nine cases were followed up and divided into two groups: the expectation group ( n=45) and the intrauterine intervention group (all underwent radiofrequency ablation, n=44) and the pregnancy outcomes were compared between the two groups. After excluding eight cases without complete ultrasound data, the expectation group was further divided into two subgroups: the pump fetus survival ( n=28) and the pump fetus death groups ( n=9), and the survival subgroup was divided into the spontaneous arrest group ( n=16) and coexistence group ( n=12) according to whether or not the blood flow stopped spontaneously.The relationship between ultrasonic indexes and pregnancy outcome was compared between the groups. Chi-square test (or Fisher's exact test), univariate logistic regression analysis and receiver operating characteristic (ROC) curve were used to analyze the relationship between the estimated acardiac to pump twin weight ratio (A/P Wt) and the pregnancy outcome of the pump twin in the expectation group. Results:(1) The median gestational age at diagnosis of the 99 TRAPS cases was 16.4 weeks (13.3- 21.3 weeks) and 32% (32/99) were diagnosed in the first trimester. Most of the cases were monochorionic diamniotic pregnancies (72/99, 73%). The survival rate of the pump twins was 71% (63/89). (2) Chromosome karyotyping and/or chromosomal microarray analysis was performed in 19 acardiac twins and 82 pump twins. The detection rate of genetic abnormalities in the acardiac twins was higher than that in the pump twins [4/19 vs 5% (4/82), Fisher's exact test, P=0.039]. Chromosomal microarray analysis was performed in 54 pump twins with normal karyotypes and the results showed three (6%) with genetic abnormalities. (3) In the expectation group, the area under ROC curve for the prenatal A/P Wt were 0.913 in predicting pump twin death and 0.807 in predicting spontaneous cessation of blood flow in the cardiac twin, and the cut-off values were 0.24 (sensitivity: 88.9%, specificity: 96.4%) and 0.11 (sensitivity: 75.0%, specificity: 81.3%), respectively. The survival rate of pump twins with abnormal cardiac function after intrauterine intervention was higher than that of the expectant group [72% (18/25) vs 3/11, Fisher's exact test, P=0.025]. Conclusions:TRAPS can be diagnosed in the first trimester and commonly occur in monochorionic diamniotic pregnancies. The detection rate of genetic abnormalities in the acardiac twins is higher than that in the pump twins. Prenatal A/P Wt>0.24 indicates the death of the pump twin and prenatal A/P Wt≤0.11 suggests a high possibility of spontaneous cessation of blood flow in the acardiac twin. Radiofrequency ablation is an effective method for improving the prognosis of the pump twin with cardiac dysfunction.

Objective: To compare the efficacy and safety of active transfer of plaque (ATP) versus provisional stenting (PS) with drug-eluting stents (DES) for the treatment of coronary bifurcation lesions. Methods: A total of 1 136 patients with bifurcation lesions hospitalized in 6 selected hospitals between January 2010 and January 2014 were included in this prospective observational trial, patients were divided into either ATP (n=560) or PS group (n=576) accordingly. The primary endpoint was target lesion revascularization within 1 year, and the second endpoints were all-cause death, cardiogenic death, myocardial infarction, stent thrombosis, stroke, recurrent angina within 1 year. Results: There were no significant differences in age, sex, hypertension, diabetes, hyperlipidemia and smoking history between the two groups (P>0.05). The incidence of TIMI blood flow <3 grade in the side branch (1.6%(9/560) vs. 7.5% (43/576), P<0.01), acute occlusion of the side branch (1.3%(7/560) vs. 7.1%(41/576), P<0.01) and implanted stents of side branch (1.8%(10/560) vs. 7.8% (45/576), P<0.01) were significantly lower in the ATP group than those in the PS group. During the one year follow up, the rate of target lesion revascularization was similar between ATP group and PS group (4.6%(26/560) vs. 4.0%(23/576), P=0.66). Conclusions The effectiveness and safetyof ATP techniquein the patients with coronary bifurcation lesions is comparable to the PS technique. However, ATP technique is superior to PS technique on effectively reducing the incidence of implanted stents in the side branch.

OBJECTIVETo perform molecular cytogenetic study on two fetuses with abnormal ultrasound findings and analyze their genotype-phenotype correlation.

METHODSG-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on amniotic fluid cells from both fetuses and peripheral blood samples from their parents. Results of SNP array were analyzed with bioinformatics software.

RESULTSG-banded karyotyping failed to detect any abnormalities in both fetuses and their parents. SNP array detected a 2.484 Mb terminal deletion at 17p13.3 [arr[hg19] 17p13.3 (83 035-2 567 405)×1] in fetus 1 and a 3.295 Mb terminal deletion at 17p13.3p13.2 [arr[hg19] 17p13.3p13.2 (83 035- 3 377 560)×1] in fetus 2. Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin. Metaphase FISH performed on amniotic fluid cells confirmed the presence of 17p13.3 and 17p13.3p13.2 deletions detected by the SNP array, while metaphase FISH performed on the parents excluded any potential chromosome rearrangements.

CONCLUSIONAbnormal ultrasound features for fetuses with MDS mainly include central nervous system anomalies. SNP array can efficiently detect 17p13.3 microdeletions underlying MDS, and accurately map the breakpoints and involved genes, which may facilitate understanding of the genotype and phenotype correlations for MDS.

Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; Classical Lissencephalies and Subcortical Band Heterotopias ; diagnostic imaging ; genetics ; Female ; Fetal Diseases ; diagnostic imaging ; genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Phenotype ; Polymorphism, Single Nucleotide ; Pregnancy ; Ultrasonography, Prenatal ; methods

OBJECTIVETo investigate the value of single nucleotide polymorphism array (SNP array) for the identification of de novo mutations in the DMD gene among fetuses.

METHODSG-banded karyotyping and SNP array were performed on a fetus with intrauterine growth restriction but without family history of Duchenne/Becker muscular dystrophy (DMD/BMD). Multiplex ligation-dependent probe amplification (MLPA) was subsequently applied on amniocytes and maternal peripheral blood sample to detect DMD gene deletion/duplication mutations.

RESULTSKaryotyping of amniocytes showed a normal 46, XY karyotype. SNP array on amniocytes detected a 116 kb deletion (chrX: 32 455 741-32 571 504) at Xp21.1 with breakpoints at introns 16 and 30 respectively, encompassing exons 17-29 of the DMD gene. In addition, MLPA analysis of the DMD gene on amniocytes confirmed the deletion of exons 17 to 29 identified by SNP array. However, no deletion/duplication mutation was detected by MLPA in the mother.

CONCLUSIONThe de novo deletion of exons 17 to 29 of the DMD gene detected in the fetus may result in BMD or DMD. SNP array can improve the efficiency for detecting genomic disorders in fetuses with unidentified pathogenic genes, negative family history and nonspecific phenotypes.

Adult ; Dystrophin ; genetics ; Exons ; genetics ; Female ; Fetus ; abnormalities ; Gene Deletion ; Humans ; Muscular Dystrophy, Duchenne ; genetics ; Phenotype ; Polymorphism, Single Nucleotide ; genetics ; Pregnancy

Objective To discuss the clinical application value of 256-slice helical CT 3D-imaging in guiding interventional occlusion therapy for patent ductus arteriosus (PDA).Methods A total of 40 patients with sonography-proved PDA were randomly divided into group A (angiography group) and group B (CT-guided group) with 20 patients in each group.For the patients of group A,occlusion of PDA was performed based on the intraoperative angiography findings;and for the patients of group B,occlusion of PDA was carried out according to CT examination results.Intraoperative cardiac ultrasound monitoring was adopted and the curative effect was evaluated.Results The morphology of PDA demonstrated on CT 3Dimaging in group B was highly consistent with the configuration of PDA displayed on intraoperative angiography in group A.The most narrow diameters of PDA in group B and group A were (3.88±1.59) mm and (3.63±1.41) mm respectively,and the lengths of PDA in group B and group A were (6.1±1.06) mm and (6.82±0.74) mm respectively;the differences between the two groups were not statistically significant (P＞0.05).The time spent for surgery in group B and group A was (34.3±9.11) min and (17.33±5.81) min respectively,and the intraoperative X-ray radiation doses in group B and group A were (33.93±11.0) mGy and (66.48±9.77) mGy respectively;the differences between the two groups were statistically significant (P＜0.001).In group B,the preoperative X-ray radiation dose from CT examination was (119.79±29.45) mGy,when it was added to the intraoperative X-ray radiation dose the total cumulative radiation dose of group B was strikingly higher than that of group A.Conclusion Contrast-enhanced 256-slice helical CT scan and 3D-imaging technique can replace intraoperative angiography to get accurate anatomical imaging information of PDA,which are very helpful for the performance of interventional occlusion of PDA,meanwhile,it can effectively reduce the damage to the punctured artery and shorten the operation time.However,the radiation dose is a factor that should be taken into consideration.(J Intervent Radiol,2017,26:206-209)

OBJECTIVETo analyze a fetus with abnormal sonographic features and correlated its genotype with phenotype.

METHODSG-banding analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed for the fetus. Karyotyping and FISH were also carried out for the parents.

RESULTSSNP array detected a 4.4 Mb deletion at 1q44 and a 10.4 Mb duplication at 17q24.3q25.3 in the fetus. Based on the results of SNP array and FISH analysis, the father was diagnosed with a cryptic t(1;17)(q44;q24.3) translocation. The fetus has inherited a der(1)t(1;17)(q44;q24.3) from its father.

CONCLUSIONThe 1q44 deletion and 17q24.3q25.3 duplication may have contributed to the abnormal sonographic features presented by the fetus.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 17 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Polymorphism, Single Nucleotide ; Pregnancy ; Translocation, Genetic ; Trisomy ; genetics ; Ultrasonography, Prenatal

OBJECTIVE To explore the mechanism and diagnostic method for monochorionic-diamniotic twins discordant for karyotype analysis. METHODS Dual amniocentesis was performed on five pairs of monochorionic-diamniotic twins, which all consisted of a normal twin and one with multiple malformations revealed by ultrasound. Karyotype analysis was performed on amniocytes derived from each of the twins. Zygosity was also determined with DNA extracted from amniocytes with 16 polymorphic microsatellite markers. RESULTS Three cases of 45,X, one case of 47,XX,+9 and one case of 47,XY,+18 were detected among the abnormal twins, while the normal fetuses all had a normal karyotype. DNA analysis suggested that, in all cases, the twins have shared the 16 polymorphic microsatellite markers, which confirmed their monozygosity. CONCLUSION Monochorionic-diamniotic twins may be discordant for karyotyping, for which anaphase lagging, chromosomal non-disjunction and trisomy rescue may be the underlying reasons. As a simple method, dual amniocentesis can be used to obtain amniotic fluid samples for karyotype analysis and determination of zygosity for such twins.
Adult ; Amniocentesis ; Chromosome Banding ; Female ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Twins, Monozygotic ; genetics

Currently, monitoring system of awareness of the depth of anesthesia has been more and more widely used in clinical practices. The intelligent evaluation algorithm is the key technology of this type of equipment. On the basis of studies about changes of electroencephalography (EEG) features during anesthesia, a discussion about how to select reasonable EEG parameters and classification algorithm to monitor the depth of anesthesia has taken place. A scheme which combines time domain analysis, frequency domain analysis and the variability of EEG and decision tree as classifier and least squares to compute Depth of anesthesia Index (DOAI) is proposed in this paper. Using the EEG of 40 patients who underwent general anesthesia with propofol, and the classification and the score of the EEG annotated by anesthesiologist, we verified this scheme with experiments. Classification and scoring was based on a combination of modified observer assessment of alertness/sedation (MOAA/S), and the changes of EEG parameters of patients during anesthesia. Then we used the BIS index to testify the validation of the DOAI. Results showed that Pearson's correlation coefficient between the DOAI and the BIS over the test set was 0.89. It is demonstrated that the method is feasible and has good accuracy.
Algorithms ; Anesthesia, General ; Decision Trees ; Electroencephalography ; Entropy ; Humans ; Intraoperative Awareness ; Monitoring, Physiologic ; Propofol

A total of 20 normal newborns and 8 brain injured newborns were monitored for 2 hours with domestic digital amplitude integrated cerebral function monitor (CFM 3000) and similar imported products LECTROMED CFM 5330 simultaneously. 32 newborns with seizures or suspected seizures were monitored with CFM 3000 and conventional electroencephalogram (EEG) simultaneously. The tracings of amplitude integrated electroencephalogram (aEEG) monitored by CFM 3000 and LECTROMED CFM 5330 are similar to each other. The continuous electrical activity, sleep-wake cycle, the mean of lower or upper bound voltage and duration of broad and narrow band were no significant statistical difference between different machines; The pattern of aEEG tracing of 8 infants with brain injury monitored by CFM 3000 was the same as monitored by the LECTROMED CFM 5330. The detection rate of seizure with CFM 3000 and conventional EEG were no statistically significant difference, and the consistency with Kappa test was: Kappa = 0.552, P = 0.001. The CFM 3000 can reflect the change of cerebral function and identify infants with brain injury reliably.
Brain Injuries ; diagnosis ; physiopathology ; Electroencephalography ; methods ; Female ; Humans ; Infant, Newborn ; Male ; Monitoring, Physiologic ; instrumentation ; methods ; standards ; Seizures ; diagnosis ; physiopathology ; Signal Processing, Computer-Assisted