OBJECTIVE: To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses. METHODS: Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201). RESULTS: A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. CONCLUSION Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
Humans ; Exome Sequencing/methods* ; Female ; Pregnancy ; DNA Copy Number Variations/genetics* ; Genetic Testing/methods* ; Prenatal Diagnosis/methods* ; Adult ; Male ; Fetus ; Bone Diseases, Developmental/diagnosis* ; Ultrasonography, Prenatal

OBJECTIVE: To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling. METHODS: One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children's Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher's exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children's Hospital (Ethics No.: QFELL-YJ-2025-85). RESULTS: Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences (P < 0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development. CONCLUSION CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; DNA Copy Number Variations/genetics* ; Kidney/abnormalities* ; Adult ; Ultrasonography, Prenatal ; Urogenital Abnormalities/diagnosis* ; Microarray Analysis/methods* ; Retrospective Studies ; Urinary Tract/abnormalities* ; Fetus ; Pregnancy Outcome ; Vesico-Ureteral Reflux

Objective:To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods:It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results:Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions:The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.

Objective:To explore the genetic etiology for a Chinese pedigree affected with Treacher-Collins syndrome (TCS) through whole exome sequencing (WES).Methods:A TCS pedigree which was diagnosed at the Women and Children′s Hospital Affiliated to Qingdao University on February 5 2020 was selected as the study subject. Following collection of clinical data, WES was carried out. Candidate variant was validated through Sanger sequencing and bioinformatic analysis..Results:The WES results showed that the proband has harbored a heterozygous c. 3337C>T variant of the TCOF1 gene, and Sanger sequencing confirmed that his mother and brother also carried the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The heterozygous c. 3337C>T variant of the TCOF1 gene probably underlay the pathogenesis of TCS in this pedigree.

Objective:To investigate the etiological characteristics of hand, foot and mouth disease (HFMD) and the VP1 gene evolution of coxsackievirus A6 (CVA6) in Qingdao from 2020 to 2022.Methods:Total enterovirus (EV), enterovirus 71 (EV71), coxsackievirus A16 (CVA16), CVA6 and coxsackievirus A10 (CVA10) were detected by fluorescent RT-PCR in throat swab samples from HFMD patients in Qingdao from 2020 to 2022. The full-length sequence amplification of VP1 gene and gene sequence determination of CVA6 isolates were performed, and the phylogenetic and molecular characteristics were analyzed by MEGA-X software.Results:The overall positive rate of enteroviruses in 1 645 samples collected during 2020-2021 was 80.73%(1 328/1 645). The proportions of EV71, CVA16, CVA6, CVA10 and other enteroviruses were 0.08%(1/1 328), 19.65%(261/1 328), 68.15%(905/1 328), 0.98%(13/1 328) and 11.14%(148/1 328), respectively. Children under 5 years old accounted for 75.68% (1 245/1 645) of all cases and 100% (2/2) of severe cases. A phylogenetic tree was constructed based on the VP1 region sequences of 45 CVA6 strains showing all strains belonging to the D3a subtype. There were 10 non-synonymous mutations of amino acids in the VP1 protein by gene evolution analysis.Conclusions:CVA6 D3a subtype is the main epidemic strain causing HFMD in Qingdao from 2020 to 2022, especially in children under 5 years old.

Objective:To determine a relationship between ultrasound shear wave elastography (SWE) and pathological lessions of renal tissues in children with chronic kidney disease (CKD).Methods:It was a cross-sectional observational study, involving children admitted to the Department of Pediatrics of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2021 with definite pathological diagnosis through kidney biopsy. The SWE was used to determine the Young's modulus (elastic modulus) of the cortex and medulla of the upper, middle, and lower poles of the kidney. The renal histopathology was classified or graded. The statistical method was used to analyze the relationship between Young's modulus of the inferior polar cortex (YM cor) and medulla (YM med) of the right kidney and renal pathology. Results:The study included 110 children with definite pathological diagnosis through renal biopsy, aged (10.1±3.4) years old (2-17 years old), with 55 males (50.0%). The body mass index was (20.6±2.4) kg/m 2, and mean arterial pressure was (95±24) mmHg. There were 94 patients (85.4%) with CKD stage 1, 8 patients (7.3%) with CKD stage 2, and 8 patients (7.3%) with CKD stage 3. There was no significant difference of YM cor and YM med in the upper and middle poles of the right kidneys, and YM med in the lower poles of right kidneys in CKD patients with different stages (all P>0.05). Both YM cor [(15.75±3.36) kPa] and YM med [(13.50±2.43) kPa] of CKD stage 3 patients were significantly higher than those of CKD stage 1 patients [(12.94±2.45) kPa, (11.88±2.23) kPa](both P<0.05). There was no significant difference of YM cor and YM med in the lower poles of right kidneys between stage 1 and stage 2 CKD patients (both P>0.05). YM cor[(17.93±3.23) kPa] and YM med [(15.50±1.48) kPa] in patients with crescentic glomerulonephritis were higher than those in patients with focal segmental glomerulosclerosis [(12.71±2.42) kPa, (11.57±2.63) kPa] and mesangial proliferative glomerulonephritis [(12.73±2.04) kPa, (11.48±2.10) kPa](all P<0.05). There was no significant difference of YM cor and YM med between focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis (both P>0.05). YM cor [(16.30±2.63) kPa] and YM med [(15.54±1.59) kPa] of Lee's Ⅳ grade of IgA nephropathy were higher than those of Lee's Ⅲ grade [(13.32±2.70) kPa, (12.57±2.50) kPa](both P<0.05), while the International Study of Kidney Disease in Children grade of purpura nephritis had no significant correlation with YM cor and YM med (both P>0.05). YM cor [(15.41±2.37) kPa] and YM med [(13.82±2.59) kPa] of interstitial fibrosis/tubular atrophy (T1/T2) group of IgA nephropathy mixed with purpura nephritis were significantly higher than those of T0 group's [(12.99±2.40) kPa, (11.79±2.05) kPa] (both P<0.05). Moreover, crescent formation (C1) group had a higher YM cor [(14.21±2.77) kPa] and YM med [(12.80±2.47) kPa] than those in C0 group [(12.73±2.15) kPa, (11.59±1.97) kPa] (both P<0.05), while YM cor and YM med were unrelated to the mesangial hypercellularity (M), endocapillary cellularity (E), segmental sclerosis or adhesion (S) indicators (all P>0.05). In lupus nephritis patients, YM cor ( r=0.744, P=0.035) and YM med ( r=0.728, P=0.009) were favorably linked with the chronic index, but not with the activity index (both P>0.05). Conclusions:Renal interstitial fibrosis/tubular atrophy and crescentic development are connected with YM cor and YM med at the lower pole of the kidney as measured by SWE. SWE can be used to assess the chronic renal lesions in children with CKD in the early and middle stages. It may develop into a new noninvasive way to assess renal pathology.

Objective:To investigate the effects of placenta previa on the surgical and pregnancy outcomes in patients with total/subtotal or segmental hysterectomy attributed to placenta accreta spectrum disorders (PAS).Methods:This study retrospectively enrolled 510 patients who gave birth and underwent total/subtotal hysterectomy or segmental hysterectomy (local implantation site) due to PAS at the third Affiliated Hospital of Guangzhou Medical University from January 1, 2017, to December 31, 2022. These subjects were divided into the placenta previa group (427 cases) and non-placenta previa group (83 cases). According to the type of hysterectomy, they were further divided into the total/subtotal hysterectomy and placenta previa subgroup (221 cases), total/subtotal hysterectomy and non-placenta previa subgroup (23 cases), segmental hysterectomy and placenta previa subgroup (206 cases), and segmental hysterectomy and non-placenta previa subgroup (60 cases). Nonparametric test or Chi-square test were used to compare the differences in the clinical features, surgical and pregnancy outcomes between different groups. Binary logistic regression was used to analyze the effects of placenta previa on the risk of additional surgical procedures and adverse maternal outcomes. Results:(1) Compared with the non-placenta previa group, the hemorrhage volume within 24 h postpartum [1 541 ml (1 036-2 368 ml) vs 1 111 ml (695-2 000 ml), Z=－3.91] and the proportion of women requiring additional surgical procedures [84.8% (362/427) vs 69.9% (58/83), χ2=10.61], with total/subtotal hysterectomy [51.8% (221/427) vs 27.7% (23/83), χ2=16.10], cystoscopy and/or ureteral stenting [60.7% (259/427) vs 31.3% (26/83), χ2=24.25], total adverse pregnancy outcomes [86.9% (371/427) vs 65.1% (54/83), χ2=17.75], hemorrhage volume>1 500 ml within 24 h postpartum [54.1% (231/427) vs 33.7% (28/83), χ2=29.94], transfusion of blood products [75.9% (324/427) vs 47.0% (39/83), χ2=28.27] were all higher in the placenta previa group (all P<0.05). Binary logistic regression analysis found that for PAS patients with hysterectomy, regardless of the hysterectomy type (total/subtotal/segmental), placenta previa was risk factor for requiring additional surgical procedures ( aOR=3.26, 95% CI: 1.85-5.72) and adverse pregnancy outcomes ( aOR=5.59, 95% CI: 2.01-6.42), even if adjusting for the confounding factors such as maternal age, number of previous cesarean sections, parity, gestational weight gain, twin pregnancy, and the use of assisted reproductive technology. (2) In patients with total/subtotal hysterectomy, the proportion of women requiring additional surgical procedures was higher in those with placenta previa [82.8% (183/221) vs 56.5% (13/23), χ2=9.11] than those without placenta previa, especially the proportion of cystoscopy and/or ureteral stenting [67.9% (150/221) vs 34.8% (8/23), χ2=9.99] (both P<0.05). However, no significant difference was found in adverse pregnancy outcomes [89.6% (198/221) vs 87.0% (20/23), χ2<0.01, P=0.972] between the two groups. In patients with segmental hysterectomy, higher proportions of women requiring additional surgery [86.9% (179/206) vs 75.0% (45/60), χ2=4.94], with adverse pregnancy outcomes [84.0% (173/206) vs 56.7% (34/60), χ2=25.31], cystoscopy and/or ureteral stenting [52.9% (109/206) vs 30.0% (18/60), χ2=9.78], vascular occlusion [94.2% (194/206) vs 71.7% (43/60), χ2=24.23], hemorrhage volume>1 500 ml within 24 h postpartum [46.6% (96/206) vs 23.3% (14/60), χ2=10.37], and transfusion of blood products [68.9% (142/206) vs 33.3% (20/60), χ2=24.73] were found in the placenta previa group (all P<0.05). Furthermore, patients with placenta previa had more hemorrhage volume within 24 h postpartum [1 368 ml (970-2 026 ml) vs 995 ml (654-1 352 ml), Z=－3.66, P<0.001] in the segmental hysterectomy subgroup. After adjusting for the confounding factors such as age, number of previous cesarean sections, parity, gestational weight gain, twin pregnancy, and the use of assisted reproductive technology, binary logistic regression analysis found that placenta previa did not increase the risk of additional surgical operations ( aOR=2.71, 95% CI: 0.99-7.42) and adverse pregnancy outcomes ( aOR=2.14, 95% CI: 0.54-8.42) in patients with total/subtotal hysterectomy but were risk factors of the two outcomes for those with segmental hysterectomy ( aOR=4.67, 95% CI: 2.15-10.10; aOR=3.80, 95% CI: 1.86-7.77). Conclusions:Placenta previa increases the risk of additional surgical procedures and adverse pregnancy outcomes in patients with total/subtotal or segmental hysterectomy caused by PAS. Appropriate preparation is required after the clinical diagnosis of PAS with placenta previa.

Objective:To investigate whether the number of previous cesarean sections affects the outcomes of patients with placental implantation disease undergoing hysterectomy.Methods:Using a retrospective cohort study design, the study samples were from the obstetric clinical database of the Third Affiliated Hospital of Guangzhou Medical University, and the study subjects were patients with placental implantation disease who underwent hysterectomy. Patients were grouped according to different previous cesarean section frequencies, and their clinical characteristics, surgical outcomes, and adverse maternal outcomes were compared in each group; The impact of previous cesarean sections on adverse outcomes in pregnant women was analyzed using multivariate logistic regression.Results:Among the 244 enrolled patients, 26 had no previous history of cesarean section (11%), 132 had a previous cesarean section once (54%), and 86 had a previous cesarean section ≥2 times (35%). There was no statistically significant difference in the usage rates of uterine artery embolization, suture hemostasis, and internal iliac artery embolization among the three groups of patients (all P>0.05). Among the adverse outcomes of pregnant and postpartum women, there was no statistically significant difference in the rates of shock, bladder injury, postpartum hemorrhage, postpartum hemorrhage >1 500 ml, admission to the intensive care unit (ICU), and transfusion of blood products among the three groups (all P>0.05). Univariate logistic regression analysis showed that the number of previous cesarean sections did not increase the risk of adverse outcomes, such as shock, postpartum hemorrhage, postpartum hemorrhage ≥1 500 ml, entry into the ICU, and transfusion of blood products. Multivariate logistic regression analysis found that the number of previous cesarean sections did not increase the risk of adverse outcomes in pregnant women. Conclusions:For patients with placental implantation disease undergoing hysterectomy, the number of previous cesarean sections may not be the main factor determining maternal outcomes. It is necessary to consider other possible influencing factors more comprehensively, including previous uterine surgery history, basic health status of pregnant women, comorbidities, and availability of medical resources.

Objective:To investigate the effect of lifestyle intervention on the clinical outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in overweight or obese patients with polycystic ovary syndrome (PCOS).Methods:This study was a non-randomized controlled trial. A total of 126 overweight or obese PCOS patients who received IVF/ICSI treatment for infertility in Shaoguan Maternal and Child Health Hospital from January 2021 to December 2022 were selected by semi-random sampling method. The patients were divided into the experimental group (39 cases) and the control group (87 cases) according to whether they received the comprehensive lifestyle intervention. The experimental group maintained a healthy lifestyle and emotional control, accepted balanced diet, performed aerobic exercise and resistance exercise regularly and quantitatively, the data changes related to body mass index were collected regularly. The control group implemented a weight loss regimen on their own, following a low-calorie diet and exercise interventions. After 2 to 3 months, both groups of patients entered the test tube cycle (the intervention duration for each patient was up to the effect and their willingness to weight loss). The baseline data, cycle characteristics and pregnancy outcomes were compared between the two groups with t test and Chi-square. And the effects of lifestyle interventions on the clinical outcomes of IVF/ICSI in overweight or obese PCOS patients were also analyzed. Results:Before the intervention, the serum level of anti-muller hormone (AMH) in the experimental group was significantly higher than that in the control group [(5.62±2.98) vs (4.47±2.64) μg/L]( P<0.05). But there were no significant differences in age, infertility years, basal follicle maturation hormone (FSH), antral follicle count (AFC), primary infertility ratio, ICSI ratio, body mass index, proportion of obese patients, abdominal circumference, waist-to-hip ratio, visceral fat area and body fat percentage between the two groups (all P>0.05). After intervention, the body mass index, proportion of obese patients, abdominal circumference, visceral fat area and body fat percentage in experimental group were all significantly lower than those before intervention [(26.56±2.92) vs (29.21±3.37) kg/m2, 25.64% vs 64.10%, (89.92±7.16) vs (95.27±7.38) cm, (78.46±15.92) vs (95.46±17.21) cm2, 33.71%±2.46% vs 36.27%±3.02%] (all P<0.05). After intervention, the visceral fat area in the control group was significantly lower than that before the intervention [(92.08±19.38) vs (98.84±19.65) cm2] ( P<0.05), and there was no significant differences in the other indexes (all P>0.05). After intervention, the total amount of gonadotropin (Gn) in experimental group was significantly lower than that in control group [(2 488.23±711.30) vs (2 935.67±854.78) U] ( t=2.301, P<0.05). Conclusion:A 2-3 month lifestyle intervention can significantly reduce the body mass index, waist circumference, visceral fat area, and body fat percentage of overweight or obese PCOS patients, as well as decrease the total amount of Gn used for ovulation induction. However, it does not show a significant improvement in clinical outcomes.

Objective:To explore the value of karyotyping and chromosomal microarray analysis (CMA) in the prenatal diagnosis of balanced translocation/inversion carriers.Methods:This was a retrospective study involving 117 balanced translocation/inversion carrier couples. Among them, 90 women had a history of spontaneous abortion(≥2 times), stillbirth, fetal multiple malformations, or giving birth to children with chromosome abnormality disease and the peripheral blood karyotyping and fluorescence in situ hybridization testing confirmed that one partner was balanced translocation/inversion carrier. The present pregnancies of these cases were spontaneous and lasted until 18-25 weeks. The other 27 cases were confirmed by chromosome examination at the present pregnancy after the indication of fetal structural abnormalities by fetal karyotyping due to advanced maternal age and abnormal ultrasound and prenatal screening results. The results of karyotyping and CMA by amniocentesis during 18 to 25 gestational weeks were all summarized and described. Results:The successful rate of both methods was 100.0% (117/117). Unbalanced and balanced translocation/inversion were detected in seven (6.0%) and 39 (33.3%) fetuses by karyotyping, respectively. CMA revealed 14 fetuses with pathogenic copy number variation (CNV) and one with variants of uncertain significance(VUS), with an anomaly detection rate of 12.8% (15/117). Among the 15 cases with CNV, 13 were related to the parental translocation/inversion, one with de novo mutation (22q11.2 microdeletion syndrome), and one Duchenne muscular dystrophy mutation carrier. Based on the results of karyotype and CMA, there were 12 fetuses with unbalanced chromosomal fragments (10.3%), 37 fetuses with balanced translocation/inversion (31.6%), and 68 fetuses with normal chromosomes (58.1%). Conclusions:The combination of karyotyping and CMA can provide more accurate prenatal genetic diagnosis when one of a couple carries balanced chromosomal translocations/inversion.