Prenatal Diagnosis最新文献_第4页

Cell-Free DNA Screening After Euploid Embryo Transfer: Concordance With Amniocentesis and Residual Aneuploidy Risk. 整倍体胚胎移植后的无细胞DNA筛查：与羊膜穿刺术的一致性和残留的非整倍体风险。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-09-16 DOI: 10.1002/pd.70249

Yao Lu, Yaqiong He, Yi Huang, Yichao Niu, Shuo Zhang, Yueping Zhang, Ting Zhang, Yun Sun

{"title":"Cell-Free DNA Screening After Euploid Embryo Transfer: Concordance With Amniocentesis and Residual Aneuploidy Risk.","authors":"Yao Lu, Yaqiong He, Yi Huang, Yichao Niu, Shuo Zhang, Yueping Zhang, Ting Zhang, Yun Sun","doi":"10.1002/pd.70249","DOIUrl":"10.1002/pd.70249","url":null,"abstract":"Objective: To assess concordance between cell-free DNA screening and invasive prenatal diagnosis after single euploid embryo transfer following pre-implantation genetic testing for aneuploidy (PGT-A), and estimate residual chromosomal risk.Method: This retrospective cohort included 1079 singleton ongoing pregnancies after PGT-A between August 2019 and March 2024. Prenatal testing comprised cell-free DNA screening alone (n = 317), amniocentesis alone (n = 500), or both tests (n = 262). Chromosomal microarray analysis of amniocytes was the reference standard.Results: In the dual-testing cohort, eight pregnancies had high-risk cell-free DNA results, of which one was confirmed as 47, XXX. One low-risk result was subsequently diagnosed as sex chromosome mosaicism. Sensitivity, specificity, positive predictive value and negative predictive value were 50.0% (95% CI, 2.7-97.3), 97.3% (94.3-98.8), 12.5% (0.6-53.3) and 99.6% (97.5-99.9), respectively. Among 762 pregnancies undergoing amniocentesis, residual confirmed aneuploidy risk after euploid embryo transfer was 0.1% (1/762). The overall yield of clinically relevant CMA findings was 0.5% (4/762), including two pathogenic microdeletions. One pregnancy loss within 7 days after amniocentesis occurred (0.1%).Conclusion: After PGT-A, cell-free DNA screening showed high negative predictive value but limited positive predictive value. These findings support risk-stratified prenatal testing, while invasive diagnosis remains indicated after high-risk screening, abnormal ultrasound, or patient preference.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1788-1795"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

When Fetal Anomalies Lead to Prognostic Clarification: An Underrecognized Application of Exome Sequencing. 当胎儿异常导致预后澄清：外显子组测序的未被充分认识的应用。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-08-16 DOI: 10.1002/pd.70239

Jonathan Rips, Hagar Mor-Shaked, Rivka Birnbaum, Avital Eilat, Natalie Goldwicht, Shay Porat, Uri Erlik, Lilach Benyamini, Hagit Daum

{"title":"When Fetal Anomalies Lead to Prognostic Clarification: An Underrecognized Application of Exome Sequencing.","authors":"Jonathan Rips, Hagar Mor-Shaked, Rivka Birnbaum, Avital Eilat, Natalie Goldwicht, Shay Porat, Uri Erlik, Lilach Benyamini, Hagit Daum","doi":"10.1002/pd.70239","DOIUrl":"10.1002/pd.70239","url":null,"abstract":"Objectives: To describe a cohort of fetuses with abnormal prenatal findings in whom exome sequencing (ES) identified genetic diagnoses that refined prognostic assessment and reduced prognostic uncertainty.Methods: We retrospectively reviewed all fetal ES studies performed at our center between 2017 and 2025 for structural or biochemical abnormalities. Cases with a definitive molecular diagnosis were identified, and those with predicted mild, isolated, transient, or treatable phenotypes were classified as having comparatively favorable prognostic implications. Clinical findings and expected postnatal outcomes were analyzed.Results: Among 1692 fetuses undergoing ES, a molecular diagnosis was identified in 291 (17%). Of these, five cases (∼2%) were considered reassuring: isolated postaxial polydactyly due to a GLI1 variant; X-linked ichthyosis (STS) in a fetus with low estriol; isolated situs inversus; CFAP52-related situs inversus totalis; and MAGED2-associated transient antenatal Bartter syndrome. In all cases, ES refined prognosis and reduced the likelihood of severe syndromic conditions, enabling clearer counseling.Conclusions: Beyond detecting severe disorders, ES may help distinguish mild or manageable conditions from complex syndromes. In selected cases, it provides meaningful reassurance, reduces uncertainty, and supports informed prenatal decision-making.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1746-1751"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell Free DNA Whole Genome in Clinical Practice: A Single Center Seven-Year Experience. 临床实践中的细胞游离DNA全基因组：单中心七年经验。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 DOI: 10.1002/pd.70268

Alissa K Prior, Lauren Taylor, Nick P Guilda, Cameron Friedman, Jane E Corteville, Angela C Ranzini

{"title":"Cell Free DNA Whole Genome in Clinical Practice: A Single Center Seven-Year Experience.","authors":"Alissa K Prior, Lauren Taylor, Nick P Guilda, Cameron Friedman, Jane E Corteville, Angela C Ranzini","doi":"10.1002/pd.70268","DOIUrl":"https://doi.org/10.1002/pd.70268","url":null,"abstract":"Objective: Cell-free DNA whole-genome screening (cfDNA-WG) is offered at our institution to patients with abnormal fetal ultrasound findings who decline diagnostic testing. We describe the cfDNA-WG performance in this clinical population.Methods: We conducted a retrospective cohort study of singleton pregnancies with abnormal fetal ultrasound findings between April 2018 and July 2024. Descriptive data were abstracted via chart review. When diagnostic testing was performed, this was compared to the cfDNA-WG results.Results: 376 subjects met the inclusion criteria. Ultrasound findings included multiple congenital anomalies (n = 123), isolated structural anomaly (n = 132), isolated soft marker (n = 63), thickened nuchal translucency (n = 50), and fetal growth restriction (n = 8). cfDNA-WG was abnormal in 24 cases (6.4%). Most abnormal results (87.5%) were common whole-chromosome aneuploidies: Trisomy 21 (n = 10), Trisomy 18 (n = 6), Trisomy 13 (n = 2), and Monosomy X (n = 3). Other abnormal results included one rare autosomal trisomy (Trisomy 22) and two copy number variants. Diagnostic testing was performed in 42 subjects (11.2%), with seven discordant results, including trisomy 8, four single-gene disorders, and two chromosomal mosaicisms.Conclusions: In this cohort with abnormal ultrasound findings, abnormal cfDNA-WG results primarily reflected common aneuploidies detectable by standard cfDNA. There were five cases with normal cfDNA-WG in fetuses with significant genetic disorders, limiting the value of normal results.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal Genetic and Sonographic Features of KBG Syndrome: A Cohort Study of 19 Fetal Cases. KBG综合征的产前遗传和超声特征：19例胎儿的队列研究。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-08-22 DOI: 10.1002/pd.70241

Xi Yang, Hongke Ding, Rong Hu, Ling Liu, Weiwei Huang, Jian Lu

{"title":"Prenatal Genetic and Sonographic Features of KBG Syndrome: A Cohort Study of 19 Fetal Cases.","authors":"Xi Yang, Hongke Ding, Rong Hu, Ling Liu, Weiwei Huang, Jian Lu","doi":"10.1002/pd.70241","DOIUrl":"10.1002/pd.70241","url":null,"abstract":"Objective: To characterize prenatal sonographic features, genomic findings from chromosomal microarray analysis (CMA) and whole-exome sequencing (WES), pregnancy outcomes, and postnatal manifestations in KBG syndrome and to provide evidence for prenatal diagnosis and genetic counseling in at-risk pregnancies.Methods: A retrospective analysis was performed on the clinical data of 19 fetuses with KBG syndrome. Sonographic findings, CMA/WES results, and pregnancy outcomes were collected, summarized, and compared with published literature.Results: CMA identified 7 fetuses with 16q24.3 microdeletions, including 5 affecting non-coding exons 1-2. WES detected 12 ANKRD11 variants, including 11 loss-of-function and 5 novel variants. The main sonographic features included fetal growth restriction (FGR, 36.8%) and increased nuchal translucency (NT, 26.3%). Ventricular septal defects, pericardial effusion, central nervous system (CNS), and renal malformations were each observed in 15.8% of fetuses, whereas skeletal abnormalities were identified in 10.5%. Multiple sonographic anomalies were observed in some individuals. Of 19 affected pregnancies, 15 were electively terminated, and 4 resulted in live births.Conclusion: KBG syndrome shows heterogeneous prenatal manifestations, with FGR and increased NT being the most prevalent. 16q24.3 microdeletions and ANKRD11 loss-of-function variants are major genetic causes. Deletions involving non-coding exons 1-2 likely result in ANKRD11 gene haploinsufficiency. A combined approach of prenatal sonography, CMA, and WES is essential for accurate diagnosis, informed counseling, and management.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1829-1838"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fetal Cranial Biometric Abnormalities: The Value of Routine Ultrasound for Early Diagnosis of Glutaric Acidemia Type 1. 胎儿颅骨生物特征异常：常规超声对1型戊二酸血症早期诊断的价值。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-05-10 DOI: 10.1002/pd.70167

Shunan Wang, Xiangli Meng, Xiaoxiao Zhang, Lulu Li, Yue Tang, Yuanyuan Kong, Qingqing Wu

{"title":"Fetal Cranial Biometric Abnormalities: The Value of Routine Ultrasound for Early Diagnosis of Glutaric Acidemia Type 1.","authors":"Shunan Wang, Xiangli Meng, Xiaoxiao Zhang, Lulu Li, Yue Tang, Yuanyuan Kong, Qingqing Wu","doi":"10.1002/pd.70167","DOIUrl":"10.1002/pd.70167","url":null,"abstract":"Objective: Glutaric acidemia type 1 (GA-1) is a severe, life-threatening organic acidemia. This study aimed to evaluate fetal ultrasound findings as early clues for GA-1.Methods: A GA-1 case identified via newborn screening in Beijing and confirmed by exome sequencing was analyzed. His prenatal ultrasound records were retrospectively reviewed. A scoping review was performed following PRISMA-ScR guidelines to identify fetal GA-1 cases with prenatal imaging data from PubMed, Embase, and Scopus. Findings were summarized using the terminology reported in the original publications.Results: In the present case, both biparietal diameter (BPD) and head circumference (HC) exceeded the 97th percentile by 32 + 1 week of gestation. At 36 + 1 week, BPD remained above the 97th percentile, while HC was near it. Genetic analysis revealed two novel heterozygous GCDH variants: c.492C > G and c.648G > A. The scoping review identified six fetal GA-1 cases. Reported prenatal abnormalities included macrocephaly (5/6), enlarged Sylvian fissures (3/6), temporal lobe hypoplasia (2/6), cerebrospinal fluid (CSF) widening in the temporal fossa (1/6), and subependymal cysts (2/6).Conclusions: Specific prenatal cranial findings, particularly fetal macrocephaly, may serve as early clues for GA-1. The diagnostic indication is strengthened when macrocephaly coexists with features such as Sylvian fissure widening. Recognition of these features could facilitate earlier identification and diagnosis of GA-1.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1821-1828"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural Variation Sequencing of 26 Amniotic Fluid Samples With Partial Gene Duplications and Postnatal Follow-Up of the Fetuses. 26例部分基因重复羊水样本的结构变异测序及胎儿的产后随访。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-06-29 DOI: 10.1002/pd.70209

Shengfang Qin, Xueyan Wang, Mengjia Yan, Yuxia He, Zhuo Zhang, Yan Yin, Jin Wang, Beibei Guo, Jing Wang, Na Xi, Zhaokai Li

{"title":"Structural Variation Sequencing of 26 Amniotic Fluid Samples With Partial Gene Duplications and Postnatal Follow-Up of the Fetuses.","authors":"Shengfang Qin, Xueyan Wang, Mengjia Yan, Yuxia He, Zhuo Zhang, Yan Yin, Jin Wang, Beibei Guo, Jing Wang, Na Xi, Zhaokai Li","doi":"10.1002/pd.70209","DOIUrl":"10.1002/pd.70209","url":null,"abstract":"Objectives: Partial gene duplications (PGDups) are a significant contributor to genetic disease. The precise genomic location and structure of PGDups are often unresolved using conventional methods, so prenatal diagnosis for PGDups is challenging, especially without ultrasound abnormalities.Methods: We retrospectively applied structural variation sequencing (SVseq) to 26 amniotic fluid samples with PGDups initially identified by chromosomal microarray or sequencing. SVseq utilized mate-pair library construction and high-throughput sequencing to map PGDup structures. Pathogenicity was classified using ACMG guidelines, followed by postnatal phenotypic follow-up.Results: SVseq deciphered the PGDup structure for all twenty-six cases. Twenty-two (84.62%) were tandem duplications (TDs), three (11.54%) chromosomal complex rearrangements (CCRs), and one (3.85%) had no duplication. Among twenty-two TDs, thirteen were extragenic (TDEG), preserving gene integrity, and were classified as benign or variants of uncertain significance (VUS). Nine were intragenic (TDIG), disrupting gene structure, and were rated pathogenic or likely pathogenic (P/LP) or VUS. Postnatal follow-up revealed obvious abnormal phenotypes in only two TDIG cases (one inherited and one de novo).Conclusion: SVseq effectively resolves PGDup location and structure, allowing confident pathogenicity assessment and clear genotype-phenotype correlation. SVseq is a robust method for prenatal PGDup evaluation that could be adopted in diagnostic protocols to improve clinical outcomes.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1732-1745"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond the Negative: Insights From Postnatal Medical Genetics Follow-Up After Nondiagnostic Prenatal Exome Sequencing. 超越消极：从非诊断产前外显子组测序后的产后医学遗传学随访的见解。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-09-04 DOI: 10.1002/pd.70244

Sophie Albert, Anne Swenerton, Kirsten M Niles, Sylvie Langlois, Jessica L Zambonin

{"title":"Beyond the Negative: Insights From Postnatal Medical Genetics Follow-Up After Nondiagnostic Prenatal Exome Sequencing.","authors":"Sophie Albert, Anne Swenerton, Kirsten M Niles, Sylvie Langlois, Jessica L Zambonin","doi":"10.1002/pd.70244","DOIUrl":"10.1002/pd.70244","url":null,"abstract":"Objective: To evaluate postnatal medical genetic reassessment and reinterpretation of prenatal exome sequencing (pES) in liveborn children with prenatally identified structural anomalies and nondiagnostic prenatal genetic testing.Method: We performed a retrospective chart review of 61 liveborn children with fetal structural anomalies who had nondiagnostic chromosomal studies and pES at a tertiary care center in British Columbia, Canada (2016-2022). We assessed postnatal medical genetics reassessment, clinical drivers of reassessment, and outcomes of selective pES reinterpretation.Results: Postnatal medical genetics reassessment occurred in 41% (25/61) of children. Most reassessments occurred in the neonatal intensive care unit within the first week of life (68%, 17/25) and were prompted by postnatal phenotype modifications in 44% (11/25). Additional clinical drivers prompting reassessment included prenatally identified variants of uncertain significance and prenatal phenotypes of multisystem structural anomalies or unexplained hydrops. Of the children reassessed postnatally, 44% (11/25) underwent pES reinterpretation. Explanatory genetic diagnoses following reassessment and pES reinterpretation were made in 27% (3/11), representing 12% (3/25) of those reassessed and 5% (3/61) of the cohort. One additional postnatal genetic diagnosis was made, which explained a portion of the postnatal phenotype but was not considered explanatory for the prenatal findings.Conclusion: Postnatal pES reinterpretation identified genetic diagnoses in carefully selected cases following medical genetics reassessment of children with nondiagnostic prenatal testing for fetal structural anomalies, supporting a structured, clinically guided approach to postnatal follow-up.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1721-1731"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytogenetic and Molecular Findings in Hydrops-Related Mirror Syndrome. 水肿相关镜像综合征的细胞遗传学和分子研究。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-09-10 DOI: 10.1002/pd.70242

Brian A Burnett, Christian M Parobek, Jessian L Munoz, Lauren E Westerfield, Kristi Poling, Cara Buskmiller, Amir A Shamshirsaz, Roopali V Donepudi, Ignatia B Van den Veyver, Magdalena Sanz Cortes, Michael A Belfort, Ahmed A Nassr

{"title":"Cytogenetic and Molecular Findings in Hydrops-Related Mirror Syndrome.","authors":"Brian A Burnett, Christian M Parobek, Jessian L Munoz, Lauren E Westerfield, Kristi Poling, Cara Buskmiller, Amir A Shamshirsaz, Roopali V Donepudi, Ignatia B Van den Veyver, Magdalena Sanz Cortes, Michael A Belfort, Ahmed A Nassr","doi":"10.1002/pd.70242","DOIUrl":"10.1002/pd.70242","url":null,"abstract":"Objective: Mirror syndrome is a rare, life-threatening condition in which maternal fluid overload mirrors fetal hydrops. Data on genetic findings in affected pregnancies are limited. We compared genetic diagnoses in hydrops cases with and without mirror syndrome.Methods: We conducted a retrospective cohort study (2012-2023) of pregnancies with non-immune hydrops at a single fetal center. Clinical data along with prenatal and postnatal genetic testing results were analyzed. Mirror syndrome was defined as fetal hydrops with new or worsening hypertension and significant maternal edema. Genetic testing rates and diagnostic yields were compared between the groups.Results: Of the 192 cases, 140 (73%) underwent genetic testing. Testing rates were similar between mirror (24/31, 77%) and non-mirror cases (116/161, 72%; p = 0.54). Abnormal findings explaining the phenotype were identified in 29% of mirror and 32% of non-mirror cases (p = 0.79). Rates of single-gene disorders, aneuploidy, and copy-number variants did not differ (p > 0.05). Most single-gene diagnoses involve cardiovascular or lymphatic pathways.Conclusion: The rates and types of genetic diagnoses were similar in hydrops cases with and without mirror syndrome. Despite limited power to detect subtle differences, these findings support a similar approach to genetic counseling and evaluation for hydrops cases with and without mirror syndrome.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1752-1759"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rare Autosomal Trisomies Detected by Noninvasive Prenatal Testing: Performance, Outcomes, and Exploratory Analysis of the Theoretical Mosaicism Ratio. 通过无创产前检测检测到的罕见常染色体三体：性能、结果和理论镶嵌比的探索性分析。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-08-22 DOI: 10.1002/pd.70237

YaXian Liu, Jie Wang, Gang Wang, Hong Dong, LiRong Zhao, LiQing Hou, XiaoHua Wang

{"title":"Rare Autosomal Trisomies Detected by Noninvasive Prenatal Testing: Performance, Outcomes, and Exploratory Analysis of the Theoretical Mosaicism Ratio.","authors":"YaXian Liu, Jie Wang, Gang Wang, Hong Dong, LiRong Zhao, LiQing Hou, XiaoHua Wang","doi":"10.1002/pd.70237","DOIUrl":"10.1002/pd.70237","url":null,"abstract":"Objective: To characterize rare autosomal trisomies (RATs) detected by genome-wide noninvasive prenatal testing (GW-NIPT), evaluate their clinical significance, and explore whether sequencing-derived parameters are associated with adverse pregnancy outcomes.Methods: This single-center retrospective cohort study included 64,889 singleton pregnancies undergoing GW-NIPT (March 2021-July 2024). RATs-positive cases were evaluated using invasive diagnostics, pregnancy outcomes, and sequence-derived markers, including a platform-specific theoretical mosaicism ratio (TMR).Results: Of 112 RATs-positive pregnancies (0.17%), 79 underwent invasive diagnosis. Positive predictive value (PPV) for fetal confirmation was 5.1% (4/79) and diagnostic yield was 8.9% (7/79) when uniparental disomy/runs of homozygosity (UPD/ROH) findings were included. Follow-up of 104 pregnancies included 63 uncomplicated pregnancies, 34 adverse pregnancy outcomes, and 7 terminations of pregnancy (TOP). In the primary analysis of 93 pregnancies, the TMR showed poor discrimination for adverse outcomes (AUC 0.643, 95% CI 0.531-0.756). TMR ≥ 0.63 was associated with adverse outcomes after adjustment (adjusted OR 3.66, 95% CI 1.33-10.05; p = 0.012).Conclusions: RATs-positive NIPT results carried clinically meaningful pregnancy risk despite low fetal confirmation rates. TMR was higher with adverse pregnancy outcomes, but overlap and poor receiver operating characteristic (ROC) performance limit standalone use. TMR should be supplementary, interpreted in the context of chromosome, diagnostic, ultrasound, and obstetric findings.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1778-1787"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trio-Exome-Based Mendelian Inheritance Error Analysis Helps Identify Uniparental Disomies and Resolve Discordant NIPT Findings. 基于三外显子组的孟德尔遗传错误分析有助于识别单亲失调和解决不一致的NIPT发现。

IF 3.1 2区医学

Prenatal Diagnosis Pub Date : 2026-10-01 Epub Date: 2026-08-12 DOI: 10.1002/pd.70238

Ting Xu, Qingwen Zeng, Xinyi Lu, Xiaoyan Huo, Huili Liu, Tingting Yang, Linlin Chen, Qianfeng Zhao, Yi Liu, Yu Sun, Bing Xiao, Wenjuan Qiu, Lei Wang, Hong Zhu, Huiwen Zhang, Yongguo Yu, Yanjie Fan

{"title":"Trio-Exome-Based Mendelian Inheritance Error Analysis Helps Identify Uniparental Disomies and Resolve Discordant NIPT Findings.","authors":"Ting Xu, Qingwen Zeng, Xinyi Lu, Xiaoyan Huo, Huili Liu, Tingting Yang, Linlin Chen, Qianfeng Zhao, Yi Liu, Yu Sun, Bing Xiao, Wenjuan Qiu, Lei Wang, Hong Zhu, Huiwen Zhang, Yongguo Yu, Yanjie Fan","doi":"10.1002/pd.70238","DOIUrl":"10.1002/pd.70238","url":null,"abstract":"Objective: Uniparental disomy (UPD), particularly heterodisomy (hUPD), is an underdiagnosed etiology in cases of fetal growth restriction (FGR) and discordant noninvasive prenatal testing (NIPT). Because conventional absence-of-heterozygosity (AOH) analysis frequently misses hUPDs, we aimed to validate a systematic Mendelian inheritance error (MIE) analysis pipeline for trio exome sequencing (trio-ES) to resolve ambiguous prenatal findings.Method: A two-stage study analyzed 1948 parent-offspring trios (postnatal and prenatal samples). A retrospective cohort (n = 992) established and validated a quantitative biparental inheritance percentage (BPI%) threshold. This workflow was prospectively applied (n = 956) to evaluate clinical utility, focusing on discordant NIPT and unexplained fetal growth restriction (FGR). Orthogonal analysis of methylation or short-tandem repeats (STR) were used to confirm identified UPD.Results: Utilizing a BPI% < 0.7 threshold, the pipeline identified 12 clinically significant UPD events. Crucially, 25% (3/12) were hUPDs missed by standard AOH analysis of exome. Prenatally, the pipeline resolved 57.1% (4/7; 95% CI: 18.4%-90.1%) of discordant NIPT cases, inferring trisomy rescue and confined placental mosaicism that explained the associated FGR. Postnatally, it unmasked 8 UPD events associated with imprinting disorders for pediatric cases.Conclusion: MIE analysis of existing trio-ES data effectively captures hUPDs missed by conventional AOH analysis. Routine integration of this pipeline resolves discordant NIPT results, explains FGR, and enables comprehensive UPD detection.","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":" ","pages":"1711-1720"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0