Objective:To evaluate the screening efficacy and clinical management strategies of cell-free fetal DNA (cffDNA) for copy number variations (CNVs) at 16p13.11-p12.3.Methods:Clinical data of 35 fetuses with high-risk indications for 16p13.11-p12.3 variations identified by non-invasive prenatal test (NIPT) at the First Affiliated Hospital of Zhengzhou University between September 2018 and December 2023 were retrospectively analyzed. Amniocentesis was performed to obtain fetal samples, followed by validation through chromosomal karyotyping and CNV-sequencing. The variant size, genetic origin, and pregnancy outcomes were systematically assessed. Statistical analysis was conducted using Pearson's Chi-square test or Fisher's exact test. Results:(1) Screening efficacy: The overall positive predictive value (PPV) of cffDNA was 45.8% (11/24), with a PPV of 4/8 for deletions and 7/16 for duplications. The false-positive rate was 54.2% (13/24), including one case complicated by a Robertsonian translocation [45,XY,rob(21;22)]. (2) Genetic characteristics: Among confirmed variants, 8/11 were inherited (six maternal duplications, one paternal deletion), while 3/11 were de novo (one deletion and two of undetermined origin). (3) Clinical outcomes: Among live births, 3/9 confirmed cases exhibited abnormal manifestations, including conductive hearing loss (one case with maternal duplication), language developmental delay (one case with 16p13.11 tetrasomy combined with trisomy), and hypotonia (one case with de novo deletion). Follow-up of false-negative or undiagnosed fetuses (22 cases) and 6/9 of confirmed cases showed no abnormalities. Conclusion:CNVs at 16p13.11-p12.3 demonstrate significant incomplete penetrance. Invasive diagnosis combined with familial analysis is recommended for cffDNA-positive cases. Genetic counseling should emphasize variant size and parental origin, and long-term neurodevelopmental follow-up mechanisms should be established for confirmed fetuses.

Objective:To evaluate the screening efficacy and clinical management strategies of cell-free fetal DNA (cffDNA) for copy number variations (CNVs) at 16p13.11-p12.3.Methods:Clinical data of 35 fetuses with high-risk indications for 16p13.11-p12.3 variations identified by non-invasive prenatal test (NIPT) at the First Affiliated Hospital of Zhengzhou University between September 2018 and December 2023 were retrospectively analyzed. Amniocentesis was performed to obtain fetal samples, followed by validation through chromosomal karyotyping and CNV-sequencing. The variant size, genetic origin, and pregnancy outcomes were systematically assessed. Statistical analysis was conducted using Pearson's Chi-square test or Fisher's exact test. Results:(1) Screening efficacy: The overall positive predictive value (PPV) of cffDNA was 45.8% (11/24), with a PPV of 4/8 for deletions and 7/16 for duplications. The false-positive rate was 54.2% (13/24), including one case complicated by a Robertsonian translocation [45,XY,rob(21;22)]. (2) Genetic characteristics: Among confirmed variants, 8/11 were inherited (six maternal duplications, one paternal deletion), while 3/11 were de novo (one deletion and two of undetermined origin). (3) Clinical outcomes: Among live births, 3/9 confirmed cases exhibited abnormal manifestations, including conductive hearing loss (one case with maternal duplication), language developmental delay (one case with 16p13.11 tetrasomy combined with trisomy), and hypotonia (one case with de novo deletion). Follow-up of false-negative or undiagnosed fetuses (22 cases) and 6/9 of confirmed cases showed no abnormalities. Conclusion:CNVs at 16p13.11-p12.3 demonstrate significant incomplete penetrance. Invasive diagnosis combined with familial analysis is recommended for cffDNA-positive cases. Genetic counseling should emphasize variant size and parental origin, and long-term neurodevelopmental follow-up mechanisms should be established for confirmed fetuses.

Objective To observe the adverse reactions of different anesthesia methods used in bronchoscopic diagnosis and treatment,and provide ideas for clinical selection of the best anesthesia methods.Methods 150 patients from June 2022 to June 2023 for bronchoscope were randomly divided into group W(atomization with lidocaine combined with intravenous sedation),group Q(laryngeal mask general anesthesia)and group H(lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia),with 50 cases in each group.Heart rate(HR),mean arterial pressure(MAP)and percutaneous arterial oxygen saturation(SpO2)values were recorded at different time points,adverse reactions during recovery,recovery time and dosage of anesthetic drugs were recorded.Results At T1 and T2,SpO2 in group W(89.4±0.7)%and(91.8±0.3)%were lower than that(99.6±0.8)%in T0,and lower than those(98.6±1.3)%and(98.5±1.6)%in group Q and(99.7±0.3)%and(98.4±1.6)%in group H,the difference were statistically significant(P<0.05).At T1 and T2,the MAP of group W were(108.5±7.8)and(105.6±7.3)mmHg,which were significantly higher than those of T0(87.5±8.6)mmHg,and higher than those of group Q(92.6±8.5)and(85.8±11.3)mmHg,respectively,higher than those(85.7±9.2)and(85.2±10.8)mmHg in group H,the differences were statistically significant(P<0.05).The MAP of group Q at T1 and T3 was(92.6±8.5)and(91.4±8.6)mmHg,respectively,higher than that of T0(87.8±7.5)mmHg,and higher than those of group H(85.7±9.2)and(86.5±7.2)mmHg,with statistical significance(P<0.05).At T1 and T2,the HR of group W was(92.7±9.6)and(91.3±9.2)times/min,higher than that of T0(72.3±8.4)times/min,and higher than those of group Q(75.3±11.6)and(78.5±12.8)times/min,respectively,and higher than those of group H(76.6±10.7)and(77.2±8.5)times/min,and the differences were statistically significant(P<0.05).The hypoxemia,arrhythmia and cough rates in group Q were higher than those in group W and group H,and the differences were statistically significant(P<0.05).The recovery time of group H was(11.5±7.2)min,which was significantly lower than that of group W(16.8±8.5)min and group Q(17.6±6.4)min,and the differences were statistically significant(P<0.05).The dosage of propofol in group H was(314.3±12.7)mg and remifentanil was(211.6±12.5)μg,both lower than those in group W(390.5±12.4)mg and(268.4±13.6)μg,and lower than those in group Q(387.6±15.2)mg and(372.5±15.3)μg.The differences were statistically significant(P<0.05).The dosage of micuronium chloride was(23.7±3.8)mg in group H,lower than(32.5±4.3)mg in group Q,and the difference was statistically significant(P<0.05).Conclusion Lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia is the best anesthesia method for bronchoscopic diagnosis and treatment,which is beneficial to respiratory management and less adverse reactions in perioperative period.

Objective:To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS).Methods:Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No.2018-YB-08).Results:Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up.Conclusion:For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.

OBJECTIVE: To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS). METHODS: Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No. 2018-YB-08). RESULTS: Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up. CONCLUSION For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.
Humans ; Female ; Pregnancy ; Chromosome Duplication ; Adult ; Prenatal Diagnosis/methods* ; Chromosomes, Human, Pair 6/genetics* ; Pregnancy Outcome ; Noninvasive Prenatal Testing/methods* ; Chromosome Disorders/genetics* ; Fetus/abnormalities*

Objective:To summarize the results of prenatal diagnosis and outcome of pregnancy of fetuses with a high risk for 6p22.1-p21.32 duplication signaled by non-invasive prenatal screening (NIPS).Methods:Clinical information, results of prenatal diagnosis and pregnancy for fetuses with a high risk for 6p22.1-p21.32 duplication were collected and analyzed. This study has been approved by the medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethic No.2018-YB-08).Results:Forty three pregnant women with a high risk for 6p22.1-p21.32 duplication were identified by NIPS, among whom 30 had accepted invasive prenatal diagnosis, and 27 fetuses were verified to be false positive. Three fetuses were found to have other chromosomal abnormalities, among whom two were rated to be likely benign CNV and 1 was rated to be likely pathogenic. Follow up of the 43 pregnant women revealed that 35 fetuses were normal after birth, 1 pregnancy was terminated, and 7 were lost to follow up.Conclusion:For pregnant women with a high risk for 6p22.1-p21.32 duplication signaled by NIPS, genetic counselor need to inform them the high false positive rate and recommend invasive prenatal diagnosis and/or ultrasound examination in order to reduce the psychological and economic burdens.

OBJECTIVE: To explore the genetic basis for a rare case with Disorder of sex development. METHODS: Clinical data of the patient was collected. Chromosomal karyotyping, SRY gene testing, whole exome sequencing (WES), low-coverage massively parallel copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and whole genome sequencing (WGS) were carried out. RESULTS: The patient, a 14-year-old female, had manifested short stature and dysplasia of second sex characteristics. She was found to have a 46,XY karyotype and positive for the SRY gene. No pathogenic variant was found by WES, except a duplication at Yp11.32q12. The result of CNV-seq was 47,XYY. FISH has confirmed mosaicism for a dicentric Y chromosome. A 23.66 Mb duplication on Yp11.32q11.223 and a 5.16 Mb deletion on Yq11.223q11.23 were found by WGS. The breakpoint was mapped at chrY: 23656267. The patient's karyotype was ultimately determined as 46,X,psu idic(Y)(q11.223)/46,X,del(Y)(q11.223). CONCLUSION The combination of multiple methods has facilitated clarification of the genetic etiology in this patient, which has provided a reference for the clinical diagnosis and treatment.
Female ; Humans ; Adolescent ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Y Chromosome ; Sexual Development ; Mosaicism

Objective:To analyze the long-term prognosis of IgA nephropathy (IgAN) with focal segmental glomerulosclerosis (FSGS) and the risk factors related to renal prognosis in children with IgAN-FSGS.Methods:A retrospective study was concluded in IgAN-FSGS children who were followed up for more than 5 years and diagnosed by renal biopsy for the first time in the Eastern Theater General Hospital from January, 2004 to December, 2018. The end-point events of the study were entering end-stage kidney disease (ESKD) or estimated glomerular filtration rate (eGFR) decreased by ≥50% from baseline, which were defined as poor renal prognosis. Baseline clinicopathologic data of IgAN-FSGS children were compared between the end-point event group and the non-end-point event group. The cumulative renal survival rate of IgAN-FSGS children was calculated by Kaplan-Meier survival analysis. The influencing factors of poor renal prognosis in IgAN-FSGS children were analyzed by Cox proportional hazards model, and the diagnostic value was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC). The diagnostic value was verified by time dependent-ROC and time dependent-AUC.Results:A total of 204 IgAN-FSGS children were enrolled in this study, of whom 132 cases were males (64.7%). The median age of renal biopsy was 16 (14, 17) years old. During a median follow-up time of 90.7 (71.7, 114.8) months, 57 cases (27.9%) reached the end-point events. Compared with the non-end-point event group ( n=147), the end-point event group ( n=57) had higher proportions of males and hypertension, higher levels of 24-hour urinary protein, serum creatinine, serum uric acid, urinary N-acetyl-β- D-glucosaminidase, urinary retinol binding protein, higher proportions of glomerular segmental sclerosis (S1) ≥25% and tubular atrophy/interstitial fibrosis (T1/T2), and lower levels of serum albumin, serum IgA, and serum IgG (all P<0.05). There was no statistical difference between the two groups in treatment (all P>0.05). Kaplan-Meier survival analysis showed that with entry of ESKD or eGFR decreased by ≥50% from baseline as the end-point events, the 5-year, 10-year, and 15-year cumulative renal survival rates in IgAN-FSGS children were 88.7%, 67.6%, and 50.7%, respectively. Multivariate Cox regression analysis showed that proteinuria >1 g/24 h ( HR=3.702, 95% CI 1.657-8.272, P=0.001), hyperuricemia ( HR=3.066, 95% CI 1.793-5.245, P<0.001), S1≥25% ( HR=2.017, 95% CI 1.050-3.874, P=0.035), T1/T2 ( HR=1.863, 95% CI 1.021-3.158, P=0.016) were the independent related factors for poor renal prognosis. ROC curve analysis showed that S1≥25% ( AUC=0.605, P=0.021, sensitivity 26.3%, specificity 94.6%), T1/T2 ( AUC=0.624, P=0.006, sensitivity 43.9%, specificity 81.0%), hyperuricemia ( AUC=0.658, P<0.001, sensitivity 52.6%, specificity 78.9%), proteinuria>1 g/24 h ( AUC=0.670, P<0.001, sensitivity 87.7%, specificity 46.3%) could accurately predict the renal outcome of IgAN-FSGS. Time dependent-ROC curve validation showed that the combined diagnosis of S1≥25%, T1/T2, hyperuricemia and proteinuria>1 g/24 h had a good predictive value for renal prognosis (3-year AUC=0.846 and 5-year AUC=0.777, respectively). Conclusions:During a median follow-up of 90.7 months, 27.9% of IgAN-FSGS children have poor renal prognosis, and the 5-year, 10-year, and 15-year cumulative renal survival rates are 88.7%, 67.6%, and 50.7%, respectively. Urinary protein >1 g/24 h, hyperuricemia, T1/T2, and S1 ≥25% are the risk factors for renal prognosis in IgAN-FSGS children.

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). METHODS: Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out. RESULTS: Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25]. CONCLUSION CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.
Humans ; Child ; Female ; DNA Copy Number Variations ; Chromosome Aberrations ; Karyotyping ; Exome Sequencing ; Disorders of Sex Development/genetics*

OBJECTIVE: To assess the value of low-depth whole-genome copy number variation sequencing (CNV-seq) for the analysis of chromosomal copy number variations among fetuses with echogenic bowel (EB). METHODS: A total of 163 fetuses were included in this study. Amniotic fluid (162 cases) or chorionic villi (1 case) were collected and subjected to CNV-seq for the analysis of CNVs. RESULTS: Thirteen (8.0%) pathogenic CNVs were detected, including 9 (5.5%) aneuploidies and 4 (2.4%) CNVs. The detection rate of the isolated EB group and combined EB group were 1.7% (1/58) and 11.4% (12/105), respectively. There was a significant difference between the two groups (P < 0.05). A Xp22.1 duplication was detected in both groups, and the fetuses were predicted as female DMD carriers and born healthy. Nine cases of aneuploidies and 2 (likely) pathogenic CNVs were identified in the combined EB group, all of them have warranted induced labor. CONCLUSION The prevalence of chromosomal aneuploidies and pathogenic CNVs in fetuses with combined EB was much higher than isolated EB, and most of them may warrant termination of pregnancy. Compared with isolated EB, more attention should be paid to combined EB, for which prenatal diagnosis and genetic counseling should be carried out in time.
Amniotic Fluid ; Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Echogenic Bowel ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis ; Technology