Birth Defects Research最新文献

{"title":"Association Between Socioeconomic Status and Major Congenital Anomalies: A Two-Sample Mendelian Randomization Study","authors":"Daniel Linares,&nbsp;Qun Miao,&nbsp;Beatriz Luna","doi":"10.1002/bdr2.2524","DOIUrl":"https://doi.org/10.1002/bdr2.2524","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traditional observational studies suggest that socioeconomic status (SES) may influence the risk of congenital anomalies; however, an association remains unclear due to residual confounding. This study used Mendelian randomization (MR) to explore the potential causal relationship between SES indicators and specific congenital anomalies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed two-sample MR analyses to explore whether three indicators of SES—educational attainment, household income, and the Townsend Deprivation Index—have a relationship with the risk of major congenital anomalies. Genetic variants associated with these SES indicators were obtained from the MRC Integrative Epidemiology Unit (IEU) OpenGWAS database, based on UK Biobank data. Genetic associations with nine categories of congenital anomalies were sourced from the FinnGen study. The primary MR method was inverse-variance weighted (IVW), with sensitivity analyses and Bonferroni correction applied to account for multiple testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prior to correction for multiple testing, higher educational attainment was associated with reduced risk of congenital heart defects (CHDs) (OR = 0.60, 95% CI: 0.41–0.88; <i>p</i> = 0.001), congenital respiratory system malformations (OR = 0.20, 95% CI: 0.06–0.62; <i>p</i> = 0.005), and musculoskeletal malformations (OR = 0.47, 95% CI: 0.29–0.76; <i>p</i> = 0.002). A lower Townsend Deprivation Index was unexpectedly associated with a higher risk of congenital digestive tract anomalies (OR = 4.53, 95% CI: 1.10–18.63; <i>p</i> = 0.036). However, after Bonferroni correction, only the association between educational attainment and CHDs remained significant (adjusted <i>p</i> = 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found limited evidence on the association between SES and congenital anomalies. Only higher educational attainment was significantly associated with reduced risk of CHDs after multiple testing correction. Further research with refined methods is needed to clarify these associations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helical Body Axis Orientations in Human Embryonic Development","authors":"Sena Fujii,&nbsp;Shigehito Yamada,&nbsp;Tetsuya Takakuwa","doi":"10.1002/bdr2.2527","DOIUrl":"https://doi.org/10.1002/bdr2.2527","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In mouse embryos, the body axis typically follows a right-handed helical pattern; however, a definitive orientation in human embryos has not been established. This study aimed to characterize the body axis orientation in human embryos (CS13–CS17) from the Kyoto Collection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Embryos were classified as right-helical (RH), left-helical (LH), and middle (M) using MRI-based morphological assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RH orientation was predominant at CS13, whereas it became comparable to LH at CS14. From CS15 to CS17, LH became dominant, nearly doubling the frequency of RH by CS15. The proportion of M-pattern embryos increased with advancing Carnegie Stages, reaching 70% at CS17. As vertebral column chondrification begins at CS17–18, these findings suggest that the helical body axis is established before chondrogenesis, particularly during CS13–CS15. Internal organ laterality (stomach, heart, intestines, and liver) appeared consistent among body axis orientations in CS15–CS17 embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results demonstrate substantial variability in human embryonic body axis orientation, in contrast to the well-defined pattern in mice, and provide insights into body axis formation in human embryos and their potential role in left–right asymmetry.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous Resolution of Molar Tissue in Complete Hydatidiform Mole With a Coexisting Fetus","authors":"Paz Ahumada-Droguett,&nbsp;Trinidad Arancibia,&nbsp;Helga Vera,&nbsp;Daniel Martin,&nbsp;Francisco Sánchez,&nbsp;Juan Carlos Bustos","doi":"10.1002/bdr2.2525","DOIUrl":"https://doi.org/10.1002/bdr2.2525","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Complete hydatidiform mole with a coexisting fetus (CMCF) is a rare form of twin pregnancy associated with high maternal and perinatal risks, posing complex diagnostic and therapeutic challenges. The standard approach ranges from termination of pregnancy to conservative management to fetal viability. Recent evidence suggests that spontaneous regression of molar tissue may occur, supporting conservative treatment in selected cases. We present a new case and discuss the clinical consequences of this phenomenon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>We report a 29-year-old woman with a history of a previous molar pregnancy who presented with CMCF during her second gestation. The diagnosis was established at 21 weeks' gestation based on ultrasound findings and an elevated beta-hCG level of 454,000 mIU/mL. After multidisciplinary counseling, expectant management was indicated with close clinical, sonographic, and biochemical surveillance. By 30 weeks, significant regression in molar tissue was observed, and by 36 weeks, the appearance on ultrasound was like a normal placenta with decreased beta-hCG levels. At 37 weeks, a cesarean section was performed, resulting in the delivery of a healthy female infant weighing 2585 g. The placenta was normal and small, necrotic-appearing placental tissue. Histopathological analysis confirmed the presence of gestational trophoblastic disease with extensive necrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the third reported case of spontaneous regression of molar tissue in CMCF, with resolution occurring in the third trimester. This finding opens a new perspective for the management of these complex pregnancies, suggesting that conservative strategies may be justified in selected patients under close surveillance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Health Insurance Claims Data to Complement the Centers for Disease Control and Prevention Surveillance System for Birth Defects","authors":"Sharon Ng,&nbsp;Jeremy P. Brown,&nbsp;Loreen Straub,&nbsp;Brian Bateman,&nbsp;Kathryn J. Gray,&nbsp;Krista F. Huybrechts,&nbsp;Sonia Hernández-Díaz","doi":"10.1002/bdr2.2523","DOIUrl":"https://doi.org/10.1002/bdr2.2523","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Birth defect surveillance can help identify temporo-spatial clusters and teratogenic signals to inform subsequent investigations or interventions. In the United States, state surveillance systems exist but collect limited information, prompting a complementary use of health insurance claims data to describe national birth defect prevalence trends and investigate signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Merative MarketScan Commercial Claims and Encounters (MarketScan) database was used to identify liveborn infants from 2016 to 2022, with linkage to maternal health care records during pregnancy. Birth defects were identified using ICD-10-CM codes recorded in the first 3 months of life, and prevalence estimates with 95% confidence intervals were generated for birth defect categories and select birth defects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study population included 943,855 liveborn infants. From 2016 to 2022, the prevalence increased for cardiac, central nervous system, ear, genital, urinary, musculoskeletal, and limb birth defect categories. Stable prevalence over the study period was observed for chromosomal, oral cleft, respiratory, gastrointestinal, vascular, and eye defects. For specific defects, we observed an increased prevalence of both ankyloglossia and lip-tie over the study period and a transient higher prevalence of omphalocele over 2017 and 2018. Within genital birth defects, we observed increasing prevalence trends for congenital malformations of the penis, while hypospadias and cryptorchidism remained relatively stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Health care utilization databases can complement existing surveillance systems by generating, confirming, or refuting signals based on ecological trends or clusters. The availability of patient information in claims databases can allow for further investigation of signals to inform birth defect etiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Correspondence “Beyond Aggregate Risk: Drug- and Organ-Specific Nuances in Counseling on Antidepressant Teratogenicity” (Tsai et al. 2025)","authors":"Eydie L. Moses-Kolko,&nbsp;Loreen Straub,&nbsp;Kelly Fung,&nbsp;Krista F. Huybrechts","doi":"10.1002/bdr2.2522","DOIUrl":"https://doi.org/10.1002/bdr2.2522","url":null,"abstract":"<p>We thank the authors for their positive feedback on our recent publication “Synthesizing cohort study results to promote knowledge transfer of safety data regarding gestational antidepressant exposure and offspring congenital anomalies: A test of concept” (Moses-Kolko et al. <span>2025</span>). We appreciate the commendation for our test-of-concept fact box that we used to illustrate a strategy to facilitate prescriber-patient communication regarding potential benefits and risks of use of antidepressants during pregnancy. The idea of a layered fact box is intriguing. Because many patient encounters are virtual, technology could indeed be harnessed to create and display digital image layers during a risk discussion (Tsai et al. <span>2025</span>).</p><p>The authors raise the important point that we mention in our discussion; that presenting pooled relative risks for overall major congenital anomalies and cardiac anomalies can obscure specific risk data regarding individual drugs as well as anomalies in specific organ systems and subsystems. As the manuscript title implies, we presented the example of gestational antidepressant exposure and the risk of major congenital malformations overall and cardiac malformations as a test of concept. We agree that it would be meaningful to extend the example we provided in the manuscript to organ-specific malformations as well as specific drugs. Ideally, there would be ample studies which minimize confounding and misclassification bias available to generate pooled risk estimates on specific drug exposure-organ malformation outcomes for use in a fact box. As we mention in the manuscript, a current challenge for summarizing data for specific drugs, for new drugs, or for rare anomalies is the paucity of high-quality evidence (Covington et al. <span>2004</span>).</p><p>The authors cite several studies they believe provide clinically actionable signals. One study is misquoted. The Huybrechts study (Huybrechts et al. <span>2014</span>) did not report an organ-specific and agent-specific increase in risk. They reported an adjusted RR of 0.94 (95% CI 0.73–1.21) for the association between paroxetine and cardiac anomalies and an adjusted RR of 0.73 (95% CI 0.49–1.09) for the association with ventricular septal defects and 1.07 (95% CI 0.59–1.93) for the association with right ventricular outflow tract obstruction, specifically.</p><p>An important direction of pharmacoepidemiology research is the harmonization across studies of exposure and outcome definitions as well as methods to address confounding and bias (Richardson et al. <span>2025</span>) to make replication and meta-analysis possible in future research. We eagerly anticipate such research advances that will generate greater confidence in drug and organ-specific signals that can be incorporated into clinical risk discussions as well as into clinically useful fact boxes.</p><p>K.F.H. reports being an investigator on grants to her institution from UCB, GSK, and","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Hormone Deficiency Disrupts Embryonic Ventral Body Wall Development and Myogenesis With Partial Recovery Following LevothyroxineTherapy","authors":"Juhi Vaishnav,&nbsp;Suresh Balakrishnan","doi":"10.1002/bdr2.2520","DOIUrl":"https://doi.org/10.1002/bdr2.2520","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ventral body wall defects (VBWDs), including omphalocele and gastroschisis, result from failed embryonic midline closure and contribute to high neonatal morbidity. While thyroid hormones (THs) are essential for morphogenesis, their role in VBWD pathogenesis is not well defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate the impact of TH deficiency on ventral body wall development in chick embryos and evaluate levothyroxine as a therapeutic intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Hypothyroidism was induced on embryonic day 3 using thiourea (2.5 mg/50 μL), a thyroid peroxidase inhibitor. A rescue group received levothyroxine (2.5 μg/50 μL) on day 5.5. Embryos were harvested on days 6 and 10 for analysis of thyroid peroxidase activity, morphology, skeletal patterning, and expression of morphogenetic (SHH, MYOD, MSX1/2), epithelial/mesenchymal (CDH1/2, VIM, TGFβ1), and apoptotic (Cleaved CASPASE 3) markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thiourea-treated embryos exhibited incomplete ventral closure, skeletal abnormalities, impaired myogenesis, and disrupted epithelial–mesenchymal transition. Gene profiling showed downregulation of SHH, MYOD, and MSX1/2, with concomitant upregulation of CDH1, VIM, TGFβ1, and Cleaved CASPASE 3. Levothyroxine administration partially restored thyroid activity, improved wall integrity, and normalized developmental gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>TH deficiency perturbs morphogenetic signaling, leading to defective mesodermal differentiation, epithelial–mesenchymal imbalance, and enhanced apoptosis. Partial rescue with levothyroxine underscores the hormone's developmental role and therapeutic relevance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TH insufficiency contributes to VBWDs by disrupting key pathways in myogenesis and tissue remodeling. Early levothyroxine supplementation may offer a strategy to mitigate endocrine-related congenital malformations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidity and Multimorbidity in Adults With Congenital Heart Disease: Findings From a Multi-Site Population-Based Study","authors":"Lorenzo D. Botto,&nbsp;Matthew R. Reeder,&nbsp;George K. Lui,&nbsp;M. Jill Glidewell,&nbsp;Wendy M. Book,&nbsp;Tessa L. Crume,&nbsp;Jesse M. DeLaRosa,&nbsp;Alfred d'Ottavio,&nbsp;Karrie F. Downing,&nbsp;Marcia L. Feldkamp,&nbsp;Daphne T. Hsu,&nbsp;Amber D. Khanna,&nbsp;Sergey Krikov,&nbsp;Nelangi M. Pinto,&nbsp;Cheryl L. Raskind Hood,&nbsp;Fred H. Rodriguez III,&nbsp;Aida S. Soim,&nbsp;Kevin J. Whitehead,&nbsp;Karen Chiswell,&nbsp;Jennifer S. Li","doi":"10.1002/bdr2.2515","DOIUrl":"https://doi.org/10.1002/bdr2.2515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population-based information on such comorbidities is scarce, reducing opportunities for prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This population-based, cross-sectional study assessed comorbid conditions in adults with CHD residing in five geographic areas in the United States (in Colorado, Georgia, New York, North Carolina, and Utah). The study included 18,672 adults aged 19 to 64 years who had a healthcare encounter between 2011 and 2013 associated with ≥ 1 CHD-related diagnosis code. Data were derived from linked clinical and administrative sources, reflecting inpatient, outpatient, and emergency department encounters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most adults with CHD experienced at least one (88.5%) and usually multiple (76%) comorbidities. Overall, noncardiac comorbidities exceeded cardiac comorbidities. The most frequent noncardiac comorbidities were endocrine/metabolic conditions (e.g., diabetes, hyperlipidemia, hypothyroidism), hypertension, and neuropsychiatric conditions (e.g., anxiety, depression). The presence and number of comorbidities varied in different sociodemographic groups. Men and older individuals experienced higher rates of many comorbidities, cardiac and noncardiac, regardless of CHD type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Preventable and treatable comorbidity and multimorbidity are common in adults with CHD, with patterns shaped by sociodemographic factors and CHD type. Reducing preventable mortality in this growing population will require sustained tracking of health metrics and coordinated, data-driven, and lifelong care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress, Challenges, and Prospects of Short-Read Genome Sequencing in Prenatal Diagnosis","authors":"Yanfei Wang,&nbsp;Xiaofan Zhu,&nbsp;Zhi Gao,&nbsp;Kong Xiangdong","doi":"10.1002/bdr2.2516","DOIUrl":"https://doi.org/10.1002/bdr2.2516","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Whole-genome sequencing (WGS) has been studied increasingly as a genetic testing technology in clinical applications, and its clinical validity has been preliminarily verified. In recent years, WGS has been employed in prenatal diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review synthesizes the current research and existing guidelines on the use of WGS for prenatal diagnosis. The methods, diagnostic scope, diagnostic rate, clinical usefulness, feasibility, limitations, and ethical issues of WGS in prenatal diagnosis are also presented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After reviewing the relevant studies, evidence indicated that WGS can improve the diagnostic rate for fetuses with abnormal development. At the same time, WGS also has significant challenges, such as a higher detection rate of variants of uncertain significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>WGS has great potential in prenatal diagnosis, but more research is needed to advance its clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTBP3 Associated With 9q32 Locus Is a Candidate Gene for Nager Syndrome","authors":"Jose Antonio Gonzalez,&nbsp;Arun Devotta,&nbsp;Chang-Soo Hong,&nbsp;Casey Griffin,&nbsp;Jean-Pierre Saint-Jeannet","doi":"10.1002/bdr2.2518","DOIUrl":"https://doi.org/10.1002/bdr2.2518","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mandibulofacial dysostosis (MFD) is a congenital disorder characterized by defects in facial bones of neural crest origin. Nager syndrome combines many features of MFD with limb defects. Mutations in <i>SF3B4</i>, a gene located on chromosome 1 that encodes a protein of the spliceosome, were identified as a cause for Nager syndrome in approximately 60% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A region of chromosome 9 (9q32) that contains 35 genes has also been linked to Nager syndrome and may account for some affected individuals for which the causes of the disease have not been identified. Because Nager syndrome belongs to a rapidly growing list of craniofacial syndromes caused by pathogenic variants of splicing factors, we focused our attention on two genes in the 9q32 region that encode factors involved in pre-mRNA processing, <i>PRPF4</i> and <i>PTBP3</i>, and analyzed their role in craniofacial development in <i>Xenopus</i> embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Loss-of-function experiments in <i>Xenopus laevis</i> embryos indicate that Ptbp3 is required while Prpf4 is dispensable for neural crest gene expression at the neurula stage, a phenotype that is partially rescued by expression of human PTBP3. At the tadpole stage, Ptbp3-depleted embryos have severely hypoplastic craniofacial cartilages, phenocopying the defects observed in Sf3b4 morphant tadpoles. Furthermore, <i>ptbp3</i> expression is significantly increased in <i>Xenopus tropicalis</i> <i>sf3b4</i> Null embryos as compared to wild-type siblings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We propose that dysregulation of PTBP3 expression may cause Nager syndrome in a subset of patients who do not have a mutation in <i>SF3B4</i>.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Unbalanced Translocation t(3;13)(q29;q34) in an Infant With Hydrocephalus.","authors":"Teresa E Fowler, Anthony R Gregg, Ryan F Bloomquist","doi":"10.1002/bdr2.2517","DOIUrl":"10.1002/bdr2.2517","url":null,"abstract":"<p><strong>Background: </strong>Copy number variations in chromosomal segments 3q29 and 13q34 are described in the literature, with varying reported phenotypic findings.</p><p><strong>Case: </strong>We report the case of a male proband found to have prenatal hydrocephalus and intrauterine growth restriction at 32 weeks gestation. Genetic testing revealed a gain of a 4.8 megabase (Mb) region of 3q29 and a loss of a 5.4 Mb region of 13q33.3q34, yielding partial trisomy 3q29 and monosomy 13q34. FISH studies suggest that this unbalanced translocation resulted from a paternal balanced translocation. Findings at birth included respiratory distress requiring intubation, small birth weight, hypotonia, coagulopathy, pelvocaliectasis, and macrocephaly, with MRI demonstrating severe cortical thinning and white matter volume loss.</p><p><strong>Conclusions: </strong>Though unbalanced translocations are highly individualized with varied phenotypes even among close relatives, this discussion of a proband and family members with translocation of chromosomes 3 and 13 contributes to published knowledge regarding these variants. We demonstrate the utility of online databases DECIPHER, OMIM, and Unique, as well as a translocation risk calculator, for understanding genetic anomalies and prognostic data for families affected by similar genetic variations.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 8","pages":"e2517"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}