OBJECTIVE: To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT). METHODS: Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). RESULTS: 71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. CONCLUSION The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; Adult ; Prenatal Diagnosis/methods* ; Noninvasive Prenatal Testing/methods*

Clinical application of serological screening and non-invasive prenatal testing (NIPT) both have difficulties to attain high detection rate and low cost. For its advantages of high detection rate, high sensitivity, simplicity, short turnaround time and low cost, digital PCR (dPCR) has provided a new choice for prenatal screening of trisomies 21, 18 and 13. To standardize the application of dPCR for prenatal screening, we have formulated this consensus by referring to relevant guidelines, expert consensus and latest literature, which has covered the basic requirements, application scope, pre-testing service, testing procedure, report interpretation, genetic counseling, and limitations for this technology.

Objective:Pediatric chronic sinusitis （CRS） is a common disease within the field of otolaryngology-head and neck surgery. Due to the immaturity of sinus development and immune competence in children, its etiology and pathophysiology are complex, and its clinical features and outcomes differ significantly from those in adult patients. Currently, there are issues in the diagnosis and treatment of pediatric CRS, particularly in areas such as antibiotic use and surgical interventions, owing to a lack of sufficient attention. In recognition of this, the Chinese Rhinopathy Research Cooperation Group developed this expert consensus based on a systematic review of the latest literatures from both domestic and international sources, with reference to the latest evidence-based medical evidence worldwide, and in combination with their own clinical experience. The consensus covers various aspects including epidemiology, predisposing factors, pathophysiology, diagnosis and differential diagnosis, as well as treatment strategies such as medical therapy and surgical intervention. It aims to standardize the clinical diagnosis and treatment of pediatric CRS, improve clinical efficacy and patient satisfaction, reduce clinical expenditures, and decrease the occurrence of adverse reactions.
Humans ; Sinusitis/therapy* ; Chronic Disease ; Child ; Consensus ; Anti-Bacterial Agents/therapeutic use*

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 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 analyze the result of prenatal diagnosis and outcome of pregnancy for fetuses with rare autosomal trisomies (RATs) suggested by non-invasive prenatal testing (NIPT). METHODS: A total of 69 608 pregnant women who underwent NIPT at Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were selected as study subjects. The result of prenatal diagnosis and outcome of pregnancy for those with a high risk for RATs were retrospectively analyzed. RESULTS: Among the 69 608 pregnant women, the positive rate of NIPT for high-risk RATs was 0.23% (161/69 608), with trisomy 7 (17.4%, 28/161) and trisomy 8 (12.4%, 20/161) being the most common, and trisomy 17 (0.6%, 1/161) being the rarest. For 98 women who had accepted invasive prenatal diagnosis, 12 fetal chromosomal abnormalities were confirmed, and in 5 cases the results were consistent with those of NIPT, which yielded a positive predictive value of 5.26%. Among the 161 women with a high risk for RATs, 153 (95%) were successfully followed up. 139 fetuses were ultimately born, with only one being clinically abnormal. CONCLUSION Most women with a high risk for RATs by NIPT have good pregnancy outcomes. Invasive prenatal diagnosis or serial ultrasonography to monitor fetal growth, instead of direct termination of pregnancy, is recommended.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Pregnancy Outcome ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Fetus ; Trisomy 18 Syndrome/genetics* ; Aneuploidy

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 explore the cause for a twin pregnancy with false negative result for 22q11.2 deletion syndrome by expanded non-invasive prenatal testing (NIPT-plus). METHODS: A pregnant woman with twin pregnancy through in-vitro fertilization and negative result of NIPT-plus was selected as the study subject. Amniocentesis was conducted after ultrasonic finding of fetal abnormalities. In addition to conventional G-banded karyotyping, copy number variation sequencing (CNV-Seq) was used to detect chromosomal microdeletion and microduplication. Clinical data of the woman were analyzed to explore the reasons underlying the false negative result. RESULTS: NIPT-plus has yielded a negative result with 11.77 Mb unique reads and 3.05% fetal fraction. Both fetuses had a normal karyotype (46,XY and 46,XX). CNV-seq indicated that one of the fetuses was normal, whilst the other was diagnosed with a 2.58 Mb deletion in the 22q11.2 region. CONCLUSION The false negative result may be attributed to the combined influence of low fetal fraction, high BMI, twin pregnancy through IVF and a relatively small deletion fragment. Ultrasonography exam following a low-risk result of NIPT-plus should not be neglected.
Pregnancy ; Female ; Humans ; Prenatal Diagnosis ; Pregnancy, Twin/genetics* ; DiGeorge Syndrome/genetics* ; DNA Copy Number Variations ; Amniocentesis

Objective:To summarize initial experience of applying nanopore third-generation sequencing detection method (nanopore sequencing) for genetic diagnosis of non-classical 21 hydroxylase deficiency (NC 21-OHD), and to explore its performance and application prospects.Methods:Clinical data of the two NC 21-OHD patients, who were hospitalized at the First Affiliated Hospital of Zhengzhou University in May 2019, were collected. Peripheral venous blood was collected and genome DNA extracted. Genetic variants was detected by nanopore sequencing and underwent bioinformatic analysis. Pathogenetic mutations in CYP21A2 gene were validated with PCR-sanger sequencing in the two patients and their parents.Results:The average reads length and sequence depth in the patient one was 12, 792 bp and 27.19×. The average reads length and sequence depth in the patient two was 13, 123 bp and 21.34×. Compound variants of c.293-13C>G/c.844G>T (p.Val282Leu) and c.332_339delGAGACTAC (p.Gly111Valfs)/c.844G>T (p.Val282Leu) were detected in these two patients, which were consistent with clinical phenotype of NC 21-OHD. Further analysis showed that c.293-13C>G mutation was inherited from her father and c.844G>T (p.Val282Leu) mutation was inherited from her mother for the patient one. The c.844G>T (p.Val282Leu) mutation was inherited from her father and c.332_339delGAGACTAC (p.Gly111Valfs) mutation from her mother.Conclusions:The heterozygous mutations in CYP21A2 gene are the cause of NC 21-OHD in these two patients. Nanopore sequencing technique is a reliable new detection method for patients with NC 21-OHD.

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