Prenatal Diagnosis最新文献

{"title":"Fetal Therapy for Congenital Pulmonary Malformations: A Prospective Population-Based National Cohort Study.","authors":"Mathilde Weber, Isabelle Monier, Makan Rahshenas, Laurent J Salomon, Nicolas Sananes, Vanina Castaigne, Véronique Houfflin-Debarge, Jean-Marie Jouannic, Jérôme Massardier, Vassilis Tsatsaris, Babak Khoshnood, Nathalie Lelong, Christophe Delacourt, Alexandra Benachi","doi":"10.1002/pd.6646","DOIUrl":"https://doi.org/10.1002/pd.6646","url":null,"abstract":"<p><strong>Objective: </strong>To assess the frequency of fetal therapy for fetuses with congenital pulmonary malformations (CPMs) and to investigate their short-term outcomes.</p><p><strong>Method: </strong>The study population included 435 singleton fetuses diagnosed with CPMs from a national population-based cohort study in France in 2015-2018. Information was obtained from medical records on CPM volume ratio (CVR), signs of compression, fetal therapy and perinatal outcomes. The characteristics and outcomes of fetuses with and without fetal therapy were compared using a univariate test.</p><p><strong>Results: </strong>Twenty six fetuses (6.0%, 95% CI: 4.1-8.6) received at least one fetal therapy including thoracoamniotic shunts only (n = 3), antenatal steroids only (n = 12), and a combination of several therapies including thoracentesis and amniodrainage, in addition to shunts and steroids (n = 11). Compared with fetuses without fetal therapy, those who did have higher CVR (1.6 ± 0.3 vs. 0.7 ± 0.04, p < 0.001) and more severe signs of compression (73.1% vs. 12.8%, p < 0.001). The proportion of live births after fetal therapy was 84.6% versus 98.5% (p < 0.001) for those without fetal therapy and the hospital mortality rate was 13.6% versus 1.0% (p = 0.004), respectively.</p><p><strong>Conclusion: </strong>A small minority of fetuses with CPMs underwent fetal therapy. These patients had a lower survival compared with those who did not receive fetal therapy.</p><p><strong>Trial registration: </strong>NCT02352207.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976399","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}

{"title":"Comparison of Amnio-Exchange With a Novel Synthetic Amniotic Fluid Versus Commercially Used Fluids for Fetal Therapy: An In Vivo Rodent Model.","authors":"Samuel Martin, Jose L Peiro, Marc Oria, Braxton Forde","doi":"10.1002/pd.6644","DOIUrl":"https://doi.org/10.1002/pd.6644","url":null,"abstract":"<p><strong>Objective: </strong>Normal Saline (NS) and Lactated Ringer's (LR) damage human amniotic epithelium in vitro when compared with a synthetic amniotic fluid (Amnio-well, AW). We sought to evaluate the effect of amnio-exchange with NS, LR, and AW in vivo.</p><p><strong>Methods: </strong>On day E17.5, pregnant rats underwent amnio-exchange with NS, LR, or AW. Fetuses in each pregnant rat that did not undergo amnio-exchange acted as controls. Amnions were harvested at E20.5 and ultrastructure evaluated via electron microscopy. Protein levels of cleaved matrix metalloproteinase 9 (MMP9) and collagen 1 (Col1a) were evaluated via Western Blot. Connexin-43 expression was evaluated via immunofluorescence (IF).</p><p><strong>Results: </strong>There was an increase in amnion microfractures and epithelial cellular shrinkage with NS and LR compared with control and AW. The cleaved MMP9/Col1 ratio was increased 3.9-fold in NS (p < 0.001) and 4.5-fold LR (p = 0.0201) relative to control, whereas AW expression was similar to control (p = 0.636). Connexin-43 was also increased on IF in NS and LR relative to AW (mean gray intensity 26.5 ± 4.5, 26.5 ± 6.7, 19.2 ± 3.4, p < 0.001).</p><p><strong>Conclusion: </strong>Amnio-exchange with NS and LR led to increased amniotic microfractures and collagen degradation compared with synthetic amniotic fluid. Larger models are warranted to validate or refute these findings.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913737","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}

{"title":"Prenatal Diagnosis of Myhre Syndrome in Two Cases: Further Delineation of the Cardiac and External Phenotype.","authors":"Jeanne Jury, Madeleine Joubert, Claudine Le Vaillant, Leïla Ghesh, Pierre-Emmanuel Séguéla, Ange-Line Bruel, Benjamin Cogné, Mathilde Nizon","doi":"10.1002/pd.6642","DOIUrl":"https://doi.org/10.1002/pd.6642","url":null,"abstract":"<p><p>Myhre syndrome is a rare genetic disease caused by recurrent gain-of-function variants in SMAD4 (Ile500Thr, Ile500Val, Arg496Cys, and Ile500Met) characterized by postnatal short stature with pseudo-muscular build, joint stiffness, variable intellectual disability, hearing loss, and a distinctive pattern of dysmorphic facial features. The course can be severe in some cases, with life-threatening cardiac and pulmonary complications caused by connective tissue involvement. These progressive features over time make early clinical diagnosis difficult but possible by astute clinicians who evaluate young children with autism or short stature and unusual appearance. Only two cases of Myhre syndrome diagnosed during the prenatal period have been reported. Here, we present a detailed description of two unrelated fetuses with Myhre syndrome, each molecularly confirmed by genome or exome sequencing, who underwent fetal examination after termination of pregnancy. One had severe intrauterine growth retardation associated with crossed fused renal ectopia, and the other one had pulmonary atresia with ventricular septal defect (a form of tetralogy of Fallot). Both had mild dysmorphic features with a wide nasofrontal angle. Our results and a systematic prenatal literature review add insight into the early natural history of Myhre syndrome and highlight the contribution of prenatal next-generation sequencing in prenatal diagnosis and the importance of fetal autopsy in Myhre syndrome.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907501","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}

{"title":"Prenatal Diagnosed Agenesis of the Corpus Callosum: Identifying the Underlying Genetic Etiologies.","authors":"Xing Wei, Luyao Cai, Luye Zhang, Jianping Chen, Yun Zhang, Meng Meng, Yingjun Yang, Xinyao Zhou, Gang Zou, Luming Sun","doi":"10.1002/pd.6641","DOIUrl":"https://doi.org/10.1002/pd.6641","url":null,"abstract":"<p><strong>Objective: </strong>To assess the genetic etiologies underlying agenesis of the corpus callosum (ACC) and its pregnancy outcomes in the era of next-generation sequencing.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on prospectively collected prenatal ACC cases in which amniocentesis was performed between January 2016 and December 2022. ACC was divided into non-isolated and isolated according to the presence or absence of ultrasound abnormalities. Chromosomal microarray analysis (CMA), karyotyping and exome sequencing (ES) were performed after genetic counseling. Pregnancy outcomes were assessed by pediatric neurosurgeons and were followed up by telephone through their parents.</p><p><strong>Results: </strong>Sixty-eight fetuses with ACC were enrolled in this study. CMA detected eight cases with pathogenic copy number variants (CNVs) and all were non-isolated ACC, with a detection rate of 11.8% (8/68). Among the CMA abnormalities, the majority (6/8) were detectable by karyotyping. ES was performed in 26 cases with normal CMA, revealing pathogenic or likely pathogenic gene variations in 12 cases (46.2%, 12/26), involving L1CMA, SMARCB1, PPP2R1A, ARID1B, USP34, CDC42, NFIA and DCC genes. The detection rates of ES in isolated and non-isolated ACC were 40% (6/15) and 54.5% (6/11), respectively. After excluding cases where pregnancy was terminated (56 cases), there were 12 live births, ranging in age from 15 months to 7 years. Of these, 91.7% (11 out of 12) demonstrated normal neurodevelopmental outcomes. Specifically, all five cases with isolated ACC and negative ES results exhibited normal neurodevelopment. The remaining six cases with favorable outcomes were all isolated ACC, among which ES identified variants of DCC and USP34 gene in one each case. The other four cases were CMA-negative and declined ES.</p><p><strong>Conclusions: </strong>We highlight the efficacy of prenatal ES in determining the genetic etiology of ACC, whether isolated or not. Favorable neurodevelopmental outcomes were observed when ACC was isolated and with normal ES results.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907500","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}

{"title":"Monocentric Study on the Performance of Noninvasive Prenatal Testing on Cell-Free DNA for the Detection of Monosomy X.","authors":"Kelly Steinfort, Erik Fransen, Bettina Blaumeiser, Katrien Janssens","doi":"10.1002/pd.6643","DOIUrl":"https://doi.org/10.1002/pd.6643","url":null,"abstract":"<p><strong>Objective: </strong>Increasing the PPV of monosomy X detected by the non-invasive prenatal test (NIPT) by discriminating a (mosaic) monosomy X genotype of fetal versus maternal origin.</p><p><strong>Methods: </strong>Out of 30,700 women referred for NIPT between January 2014 and December 2021, 79 had a high risk result for 45,X. Discrimination between fetal and maternal 45,X was made based on the values for ffX, ffY and SeqFF. Follow-up was provided through analysis of amniotic fluid, maternal blood, umbilical cord blood, neonatal blood and/or placental biopsies.</p><p><strong>Results: </strong>Follow-up data were available for 70/79 women; after exclusion of one twin pregnancy, 69 pregnancies were evaluated (87.3%). Forty one of those were correctly predicted as being maternal or fetal, for an overall PPV of 59.4% (95% confidence interval [CI] 47%-71%). Of the 33 predicted fetal cases with follow-up, 11 were indeed of fetal origin, equating to a PPV of 33.3% (95% CI 18%-52%); three additional cases turned out to be placental in origin, six were maternal and for 13, no explanation could be found. The PPV of maternal cases was 88.2% (30/34 cases with follow-up correctly predicted; 95% CI 73%-97%). One case turned out to be fetal; for the other three, follow-up studies failed to prove the presence of monosomy X. Two cases for which no prediction on the origin of the monosomy X could be made (inconclusive high-risk NIPT result) turned out to have confined placental mosaicism.</p><p><strong>Conclusion: </strong>Although the PPV for fetal monosomy X remains lower than for the common trisomies, the total PPV for 45,X screening with NIPT can be improved by discerning fetal from (mosaic) maternal 45,X genotype. Thorough follow-up to determine the origin of the aberrant NIPT result is advised, so that women can be adequately counseled on the risk in their current and future pregnancies and, in case of maternal mosaic monosomy X, of their own prospects.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898097","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}

{"title":"A capture-based method of prenatal cell-free DNA screening for autosomal recessive non-syndromic hearing loss.","authors":"Qian Mu, Ling Bai, Bing Xu, Huawen Du, Zhaoyun Jiang, Shasha Huang, Bo Gao, Qixi Wu, Hanqing Zhao, Pu Dai, Yi Jiang","doi":"10.1002/pd.6550","DOIUrl":"10.1002/pd.6550","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop and validate a prenatal cell-free DNA (cfDNA) screening method that uses capture-based enrichment to genotype fetal autosomal recessive disorders. This method was applied in pregnancies at high risk of autosomal recessive non-syndromic hearing loss (ARNSHL) to assess its accuracy and effectiveness.</p><p><strong>Methods: </strong>This assay measured the allele counts in both white blood cell DNA and cfDNA from the blood samples of pregnant women using a capture-based next-generation sequencing method. It then applied a binomial model to infer the fetal genotypes with the maximum likelihood. Ninety-four pregnant couples that were carriers of variants of ARNSHL in GJB2 or SLC26A4 were enrolled. The fetal genotypes deduced using this screening method were compared with the results of genetic diagnosis using amniocentesis.</p><p><strong>Results: </strong>Of the 94 couples, 65 carried more than one variant, resulting in 170 single-nucleotide polymorphism (SNP) loci to be inferred in the fetuses. Of the 170 fetal SNP genotypes, 150 (88.2%) had high confidence calls and 139 (92.7%) of these matched the genotypes obtained by amniocentesis result. Out of the remaining 20 (11.8%) cases with low-confidence calls, only 14 (70.0%) were concordant with genetic diagnosis using amniocentesis. The concordance rate was 100% for sites where the maternal genotype was wild-type homozygous. The discordance was site-biased, with each locus showing a consistent direction of discordance. Genetic diagnosis identified a total of 19 wild-type homozygotes, 46 heterozygotes, 19 compound heterozygotes, and 10 pathogenic homozygotes. This screening method correctly genotyped 81.9% (77/94) of fetuses and demonstrated a sensitivity of 89.7% and a specificity of 89.2% for correctly identifying ARNSHL.</p><p><strong>Conclusion: </strong>This capture-based method of prenatal screening by cfDNA demonstrated strong potential for fetal genotyping of autosomal recessive disorders.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132387","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}

{"title":"Further exploration of cardiac channelopathy and cardiomyopathy genes in stillbirth.","authors":"Maja Dolanc Merc, Urška Kotnik, Borut Peterlin, Luca Lovrecic","doi":"10.1002/pd.6616","DOIUrl":"10.1002/pd.6616","url":null,"abstract":"<p><strong>Objective: </strong>To explore genetic variation including whole genome copy number variation and sequence analysis of 98 genes associated with pediatric or adult cardiomyopathies, cardiac channelopathies, and sudden death in an unexplained intrauterine fetal death cohort.</p><p><strong>Methods: </strong>The study population included 55 stillbirth cases that remained unexplained after thorough postmortem examination, excluding maternal, fetal, and placental causes of stillbirth. Molecular karyotyping was performed in 55 cases and the trio exome sequencing approach was applied in 19 cases.</p><p><strong>Results: </strong>The analysis revealed six rare variants with predicted effects on protein function in six genes (CASQ2, DSC2, KCNE1, LDB3, MYH6, and SCN5A) previously reported in cases of stillbirth or severe early onset pediatric cardiac related phenotypes. When applying strict American College of Genetics and Genomics classification guidelines, these are still variants of uncertain significance.</p><p><strong>Conclusions: </strong>Several potentially stillbirth-related genetic variants were detected in our cohort, adding to the growing literature on cardiac phenotype gene variation in stillbirth. However, the mechanisms of action, gene-gene interaction, and contribution of the uterine environment are still to be deciphered. In order to advance our knowledge of the genetics of unexplained fetal death, there is an evident need for international collaboration and field standardization.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176233","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}

{"title":"Inconsistencies between prenatal diagnostic and genetic testing laboratories on variant validation of rare monogenic diseases.","authors":"Liling Lin, Ying Zhang, Hong Pan, Jingmin Wang, Yu Qi, Yinan Ma","doi":"10.1002/pd.6628","DOIUrl":"10.1002/pd.6628","url":null,"abstract":"<p><strong>Background: </strong>The advent of next-generation sequencing (NGS) has enhanced the diagnostic efficacy for monogenic diseases, while presenting challenges in achieving consistent diagnoses.</p><p><strong>Method: </strong>We retrospectively analyzed the concordance rate and reasons for the inconsistency between the original diagnostic result from the genetic testing laboratory and the variant validation result from the prenatal diagnostic center. The validation procedure comprised three stages: validation of variant detection, reevaluation of variant classification, and assessment of recurrence risk, which involved verifying the mode of inheritance and parental carriage.</p><p><strong>Result: </strong>In total, 17 (6%) of the 286 families affected by rare monogenic diseases showed different results during the variant validation procedure. These cases comprised four (23.5%) with variant detection errors, 12 (70.5%) with inconsistent interpretation, and one (6%) with non-Mendelian inheritance patterns. False-positive NGS results confirmed by Sanger sequencing were related to pseudogenes and GC-rich regions. The classification of the 17 variants was altered in the 12 cases owing to various factors. The case with an atypical inheritance pattern was originally considered autosomal recessive inheritance, but was diagnosed as maternal uniparental disomy after additional genetic analysis.</p><p><strong>Conclusion: </strong>We underscored the significance of variant validation by prenatal diagnostic centers. Families affected by monogenic diseases with reproductive plans should be referred to prenatal genetic centers as early as possible to avoid different results that may postpone subsequent prenatal diagnosis.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427432","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}

{"title":"Perspectives of pregnant women on broadening the scope of noninvasive prenatal testing from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes: A qualitative study.","authors":"Ellis C Becking, Lidewij Henneman, Neeltje M T H Crombag, Janneke Bertorotta, Ylana Rijsbergen, Caroline J Bax, Elsbeth van Vliet-Lachotzki, Peter G Scheffer, Mireille N Bekker","doi":"10.1002/pd.6621","DOIUrl":"10.1002/pd.6621","url":null,"abstract":"<p><strong>Objective: </strong>To explore the perspectives of pregnant women on broadening the scope of noninvasive prenatal testing (NIPT) from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes.</p><p><strong>Methods: </strong>Four online focus groups (n = 23 participants) and 14 individual semi-structured interviews were conducted. Participants included pregnant women with and without a history of adverse pregnancy outcomes.</p><p><strong>Results: </strong>Both women at low and high risk of adverse pregnancy outcomes had a positive attitude towards using NIPT to predict adverse pregnancy outcomes. Perceived benefits included the possibility to potentially improve maternal and foetal outcomes by taking risk-reducing measures and/or intensified monitoring during pregnancy and the ability to mentally prepare for the potential adverse outcome. Perceived concerns included anxiety and stress caused by a high-risk test result, a false sense of control over pregnancy, and potential false reassurance. Additionally, women reasoned that broadening the scope of NIPT could increase the complexity of prenatal screening and raised concerns on the combined screening aims in one test (prediction of adverse pregnancy outcomes to improve foetal and maternal health vs. screening for foetal aneuploidies to increase reproductive autonomy). On a societal level, considerations on the risk of medicalising pregnancy and overall pressure to opt for NIPT were mentioned.</p><p><strong>Conclusion: </strong>In general, pregnant women have a positive attitude towards broadening the scope of NIPT to the prediction of pregnancy outcomes, although some concerns are acknowledged.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321445","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}

{"title":"Discovery of pathogenic variants in EFEMP2 and RAG1 and undetectable fetal phenotype: A challenge of prenatal exome sequencing.","authors":"Maud Favier, Rodolph Dard, Guillaume Gorincour, Aude Tessier, Emmanuelle Motte-Signoret, Clemence Duvillier, Caroline Racine, Laurence Faivre, Christel Thauvin-Robinet, Frédéric Tran Mau-Them","doi":"10.1002/pd.6629","DOIUrl":"10.1002/pd.6629","url":null,"abstract":"<p><strong>Background: </strong>Exome sequencing in prenatal context confronts with pathogenic variants associated with phenotypes that are not detectable prenatally.</p><p><strong>Materials and methods: </strong>A consanguineous couple was referred at 24 weeks of gestation for prenatal genetic investigations after ultrasonography findings including decreased fetal movements, hypoplastic male external genitalia, retrognathia, prefrontal edema, anomalies of the great vessels with pulmonary atresia and dilated tortuous aorta.</p><p><strong>Result: </strong>Prenatal trio exome sequencing identified two homozygous likely pathogenic variants, i.e. a missense in EFEMP2 involved in cutis laxa and a nonsense in RAG1 involved in several types of severe combined immunodeficiency.</p><p><strong>Discussion: </strong>The fetal ultrasonographic phenotype was partially compatible with previously reported prenatal presentations secondary to EFEMP2 biallelic variants, but prenatal presentations have never been reported for RAG1 related disorders because the RAG1 phenotype is undetectable during pregnancy.</p><p><strong>Conclusion: </strong>Both EFEMP2 and RAG1 variants were disclosed to the couple because the EFEMP2 variant was considered causative for the fetal ultrasonographic phenotype and the RAG1 variant was considered a finding of strong interest for genetic counselling and monitoring of future pregnancies following the American College of Medical Genetics and Genomics recommendations about the discovery of incidental findings in fetal exome sequencing in prenatal diagnosis.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458824","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}