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PubMed2026

Lineage-associated differences in adenine methylation patterns of mammalian-associated Campylobacter fetus isolates: a possible role for epigenetic factors in host tropism and pathogenesis.

Mammalian Campylobacter fetus (CF) is divided into two subspecies, C. fetus fetus (CFF) and C. fetus venerealis (CFV), the latter being bovine-adapted and responsible for the notifiable disease bovine genital campylobacteriosis (BGC). Differentiation between CF subspecies has traditionally been undertaken by a few biochemical tests, but these are complicated by the existence of a biotype, C. fetus venerealis intermedius (CFVi), which shares attributes of both CFF and CFV. Molecular methods targeting specific genes have gained acceptance for more accurate subtype identification and align well with whole-genome analysis. However, limited genomic diversity between subtypes has confounded efforts to understand the genetic basis for differential host tropism and pathogenesis of these organisms. A previous study of a small cohort of C. fetus isolates suggested that dam gene coding variations might correlate with CF subtype. Accordingly, this study examines a cohort of 331 C. fetus genomes, representative of all seven phylogenetic groups for their complement of adenine methylases and the genomic motifs they target in representative isolates. All CF isolates retained a cfeM1 gene, the presence of which correlates with RAATTY methylation, while seven other adenine methylase genes exhibited distinct cladal distributions. Notably, a cjeM1 gene appears to target the CCAN7TAG/CTAN7TGG motif in CFV and CFVi isolates only. Given the increasing recognition of the impact of adenine methylation on bacterial-host interactions, further exploration of the role of adenine methylation in C. fetus pathogenesis could reveal mechanisms contributing to BGC and thus aid in its eradication.IMPORTANCECampylobacter fetus remains an important zoonotic pathogen, for which a better understanding of its host tropism and pathogenesis is sought. However, the limited genomic variation observed between subtypes has to date confounded efforts in this regard. This study suggests that an alternative approach that examines epigenetic differences between subtypes, specifically adenine methylation patterns, may reveal mechanisms critical to the pathologies of these organisms.

Animals↗

PubMed2026

[Genetic analysis of a fetus with Short-rib thoracic dysplasia 8 with or without polydactyly due to variants of DYNC2I1 gene].

OBJECTIVE: To investigate the clinical characteristics of a fetus with Short-rib thoracic dysplasia 8 with or without polydactyly (SRTD8) due to variants of DYNC2I1 gene. METHODS: A fetus identified to have short ribs, short long bones, and narrow thorax at 26+1 weeks of gestation at the Women and Children's Hospital of Ningbo University in September 2024 was selected as study subject. The fetus underwent termination of pregnancy at 35+5 weeks of gestation. Clinical data of the fetus were retrospectively collected. Whole exome sequencing (WES) was carried out on fetal tissue, and candidate variants were validated by Sanger sequencing. Difference between the wild type and variant DYNC2I1 proteins was analyzed using AlphaFold v3.0.1 and PyMOL v2.5.6 software. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using keywords such as "DYNC2I1 gene", previous literature on patients due to biallelic DYNC2I1 gene variants were retrieved from the PubMed databases, CNKI, and Wanfang Data Knowledge Service Platform, and the genetic variant and clinical phenotypes of patients were analyzed. The literature retrieval time was set from the establishment of database to December 31, 2025. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-094). RESULTS: Prenatal ultrasound revealed that the fetus had short ribs, short long bones, and narrow thorax at 26+1 gestational weeks. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the DYNC2I1 gene, namely c.265_268 (p.Gln89GlyfsTer15) in exon 3 and c.1777C>T (p.Arg593Trp) in exon 14, which were inherited from his father and mother, respectively. Prediction of the DYNC2I1 protein structure suggested that the c.265_268del variant has formed a premature termination codon, which may significantly alter the protein's secondary structure. The c.1777C>T variant may disrupt the electrostatic interaction between Arg593 and Asp729. Based on the ACMG guidelines, the c.265_268del (p.Gln89GlyfsTer15) variant was predicted to be likely pathogenic (PM2_Supporting +PVS1), whilst the c.1777C>T(p.Arg593Trp) variant was rated as uncertain significance (PM2_Supporting+PM3+PP4). Literature search has identified five articles related to biallelic DYNC2I1 variants involving a total of 11 fetuses/patients. Together with the fetus from this study, typical phenotypes included short ribs (6 cases), narrow thorax (6 cases), short limb bones (6 cases), and hand polydactyly (6 cases), and foot polydactyly (5 cases), albeit with significant clinical heterogeneity. A total of 12 genetic variants were identified, among which c.44delC was the most common (16.7%, 4/24), followed by c.1777C>T, c.2246C>T, and c.2305G>A (each accounting for 12.5%). No mutational hotspot was identified. CONCLUSION: The c.265_268del (p.Gln89GlyfsTer15) and c.1777C>T (p.Arg593Trp) compound heterozygous variants of the DYNC2I1 gene probably underlay the pathogenesis of SRTD8 in this fetus. This study has enriched the mutational spectrum of the DYNC2I1 gene and facilitated etiological diagnosis and treatment of DYNC2I1-related diseases.

Humans↗

PubMed2026

A novel PKHD1 missense variant disrupting splicing in a fetus with Caroli disease.

BACKGROUND: Caroli disease (CD) is a rare inherited disorder characterized by dilatation of intrahepatic bile ducts, and prenatal diagnosis of this disease is extremely rare. PKHD1 is the only known causative gene, yet the pathogenicity of most missense variants remains unclear. METHODS: Exome sequencing (ES) was performed on a fetus with clinical features of CD. Candidate variants were validated by Sanger sequencing in the family. The impact of the novel missense variant on pre-mRNA splicing was assessed using minigene assays, and structural modeling of the PKHD1 protein was conducted with AlphaFold 3. RESULTS: At 23 weeks of gestation, the fetus showed hepatic cysts on ultrasound and a "central dot" sign on MRI, suggesting a diagnosis of CD. The fetus also exhibited features of autosomal recessive polycystic kidney disease and oligohydramnios. ES identified and Sanger sequencing confirmed three PKHD1 variants: a paternal nonsense variant c.5323C>T; p.(Arg1775*), and two maternal missense variants c.6682G>C; p.(Glu2228Gln) and c.8012G>T; p.(Arg2671Leu). The variant c.6682G>C is novel and minigene assays demonstrated that it caused exon 40 skipping, leading to an in‑frame deletion (c.6491_6682del; p.(Gly2164_Arg2227del)). Structural modeling predicts that this deletion lies within a large β‑barrel domain and may compromise its structural stability. Conclusion We characterize a novel missense variant that causes aberrant splicing of PKHD1 in CD. This finding underscores the necessity of functional analysis for evaluating the pathogenicity of missense variants, especially those at the last nucleotide of an exon. Our study expands the mutation spectrum of PKHD1 and provides insights into genotype‑phenotype correlations.

Humans↗

PubMed2025

Molecular Detection and Characterization of Bovine Diarrhea Virus (BVDV) in Aborted Fetuses and Semen Samples from Paraguay.

Bovine viral diarrhea virus (BVDV) is the most prevalent pathogen in cattle and causes significant economic losses due to its severe clinical manifestations. It belongs to the family Flaviviridae and is distributed in species A, B, and H within the genus Pestivirus. The objective of this study was to detect and characterize BVDV using molecular techniques (RT-PCR) in semen and aborted fetuses samples that were sent to the CEDIVEP (Veterinary Diagnostic Center of Paraguay) laboratory. Seventy-three samples of semen from bulls were analyzed, and 54.7% of the samples were positive for Pestivirus A. The presence of Pestivirus A and H was detected in 2/8 spontaneously aborted fetuses. The genotypes of four individual samples of type A and four samples of type H organs were confirmed by partial sequencing of the 5-UTR region. The presence of BVDV was confirmed by molecular techniques for the first time in our country through its detection in different types of samples, as well as the presence of two genotypes. This suggests that the circulation of this virus can cause significant losses in cattle production in Paraguay.

Diarrhea Viruses, Bovine Viral↗

PubMed2026

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

BACKGROUND: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably resulted in little to no difference in severe intraventricular haemorrhage (grade 3 or 4) (RR 0.81, 95% CI 0.64 to 1.04; 6 RCTs, 6542 infants; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

Humans↗

PubMed2026

Detecting Androgenetic Origin of the Genome via Single-Nucleotide Polymorphism-Based Cell-Free DNA Screening in Dichorionic Diamniotic Twin Pregnancies With Complete Hydatidiform Moles and a Coexisting Normal Fetus: A Three-Case Report.

What is already known about this topic? ◦. Complete hydatidiform mole with a coexisting normal fetus (CHMCF) refers to a pregnancy in which a normal fetus and a complete mole coexist. ◦. CHMCF is associated with substantial maternal and fetal morbidity, including hemorrhage, severe anemia, hypertensive disorders, hyperthyroidism, prematurity, fetal loss, and an increased risk of gestational trophoblastic neoplasia. What does this study add? ◦. We report three cases of dichorionic diamniotic (DCDA) twin pregnancies with suspected CHMCF, in which single‐nucleotide polymorphism (SNP)–based cell‐free DNA (cfDNA) analysis detected the androgenetic origin of the genome implying concurrent presence of paternal uniparental diploidy and biparental diploidy in maternal plasma. ◦. To our knowledge, this is among the first case series applying SNP‐based cfDNA prospectively in this specific clinical scenario in twin pregnancy. Its prospective dual‐component detection in twins has a potential clinical decision impact on CHMCF.

Journal Article↗

PubMed2026

Perinatal Diagnosis of Generalized Arterial Calcification of Infancy: First Genetically Confirmed ENPP1 Case in an Egyptian Fetus.

Generalized Arterial Calcification of Infancy (GACI) is a rare genetic vascular disease characterized by the early onset (between in utero and infancy) of extensive calcification and stenosis of the large and medium-sized arteries. Presentation is typically with respiratory distress, congestive heart failure, and systemic hypertension. With approximately 300 cases reported worldwide in the medical literature. The prevalence is unknown; however, based on the carrier frequency of the recognized pathogenic variants, a frequency of 1 in 200,000 has been suggested. The autosomal recessive form of GACI disorder is caused by mutations in the ENPP1 or ABCC6 genes. To the best of our knowledge, this study represents the first genetically confirmed case of GACI in an Egyptian fetus detected during the perinatal period. In this report, we describe a case of GACI in a fetus with a pathogenic ENPP1 gene mutation at 29 weeks of gestation. Ultrasound examination revealed aortic and pulmonary valve stenosis, biventricular hypertrophy, and a hypercalcified aorta and ductal arch. Genetic testing identified a homozygous pathogenic variant in the ENPP1 gene: c.749C>T (p.Pro250Leu). In conclusion, early diagnosis of GACI is vital due to its severe prognosis and early symptom onset. Expert fetal echocardiography plays a key role in detecting arterial calcification during pregnancy. Genetic testing enhances diagnostic accuracy, informs treatment strategies, and supports family counselling.

Arterial calcification↗

PubMed2026

Prenatal exome sequencing of fetuses with central nervous system anomalies based on prenatal ultrasound and magnetic resonance imaging diagnosis: A retrospective cohort study with a systematic review and meta-analysis.

INTRODUCTION: Fetal central nervous system (CNS) abnormalities have diverse etiologies, with genetic factors as a major contributor. Prenatal exome sequencing (ES) is a powerful tool for precise molecular diagnosis of CNS anomalies, but its diagnostic yield varies among studies. This study aimed to evaluate the additional diagnostic yield of prenatal ES compared with chromosomal microarray analysis (CMA) in fetuses with CNS anomalies detected by prenatal imaging. MATERIAL AND METHODS: We collected ES results from fetuses diagnosed with CNS anomalies by prenatal imaging (2019-2024) who had negative results. Subgroup analyses assessed phenotype-specific ES diagnostic yield for associated genes and variants. A systematic review and meta-analysis incorporating our data and published studies further explored the association between phenotype and diagnostic yield. RESULTS: In the cohort study of 219 cases, ES identified pathogenic/likely pathogenic single nucleotide variations in 36 cases (16%). The highest diagnostic yield of ES was in cases with multisystem malformations (25%, 14/55), followed by multiple CNS anomalies (15%, 2/13) and isolated CNS anomalies (13%, 20/151). The most commonly identified isolated CNS anomaly was agenesis of the corpus callosum (31%, 5/16). Neural tube defects with urogenital anomalies were associated with a positive ES finding in 57% (4/7) of cases. The meta-analysis of 989 cases from 22 studies showed a pooled diagnostic yield of ES of 27% (95% CI, 21%-34%). The highest diagnostic yield of ES was in cases of corpus callosum anomalies with facial abnormalities (75%, 8/11) and neural tube defects with urogenital malformations (80%, 12/15). The diagnostic yield of ES for three or more CNS abnormalities was 43% (95% CI, 31%-58%), significantly higher than that for only two abnormalities (10%, 95% CI, 4%-18%). No significant difference in diagnostic yield was found between cases identified by prenatal MRI combined with ultrasound (27%, 95% CI, 20%-36%) and those identified by ultrasound alone (25%, 95% CI, 17%-35%). CONCLUSIONS: ES provided a significantly higher diagnostic yield than CMA for fetal CNS abnormalities, with diagnostic yields varying by phenotype. The systematic review and meta-analysis confirmed that the complexity and combination of malformations are key factors associated with differences in ES diagnostic yield.

Humans↗

PubMed2026

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved ∼80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

Humans↗

PubMed2026

Paediatric outcomes after maternal nipocalimab for haemolytic disease of the fetus and newborn: an open-label, single-arm study.

OBJECTIVES: To describe haemolytic disease outcomes, growth, neurodevelopment and health-related quality of life (HRQoL) through 24 months of life in infants exposed to nipocalimab in pregnancies at high risk of early-onset severe haemolytic disease of the fetus and newborn (EOS-HDFN). DESIGN: A multicentre, open-label, single-arm trial. SETTING: Centres with expertise in HDFN management. PATIENTS: Pregnant individuals with previous EOS-HDFN and maternal anti-D titres ≥32 or anti-K titres ≥4. INTERVENTIONS: Weekly nipocalimab (30 and/or 45 mg/kg) from 14 to 35 gestational weeks. MAIN OUTCOME MEASURES: Infants' cord-blood alloantibody titres at birth, HDFN management, growth through 6 months, neurodevelopment (caregiver-reported Ages and Stages Questionnaire, third edition (ASQ-3)) and HRQoL assessments through 24 months of life. RESULTS: Of 13 pregnancies, 12 resulted in live births; one fetal loss occurred due to intrauterine transfusion (IUT) complications. A single simple transfusion was administered in one of seven infants delivered after a maternal nipocalimab course without IUTs, where cord blood alloantibody titres were <8. Multiple transfusions (one to seven simple transfusions/infant; one exchange transfusion) were administered to five infants delivered after early nipocalimab discontinuation and IUTs, with cord-blood alloantibody titres ranging from 512 to 32 768. No unusual growth patterns were observed through 6 months. No neurodevelopmental delays were identified through 24 months of life, with mean ASQ-3 domain scores within normal ranges. HRQoL outcomes were positive across physical, emotional, social and cognitive functioning. CONCLUSIONS: Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life. TRIAL REGISTRATION NUMBER: NCT03842189.

Child Health↗

PubMed2026

The Same Homozygous Pathogenic Variant in CHAT Underlies Lethal Fetal Akinesia Syndrome in Three Xhosa South African Fetuses.

What is already known about this topic? ◦. Biallelic pathogenic variants in CHAT cause congenital myasthenic syndrome (CMS), typically presenting postnatally with episodic apnea and neuromuscular weakness. CHAT encodes choline acetyltransferase, essential for acetylcholine synthesis at the neuromuscular junction, and previously has not been associated with uniformly lethal prenatal phenotypes. What does this study add? ◦. We demonstrate that biallelic CHAT variants can cause severe fetal akinesia resulting in lethal multiple pterygium syndrome, expanding the phenotypic spectrum to include presentation, lethality and supporting inclusion of CHAT in fetal akinesia gene panels.

CHAT↗

PubMed2024

Prenatal diagnosis and molecular cytogenetic analysis of pure chromosome 10p15.3 microdeletion using chromosomal microarray analysis.

BACKGROUND: The literature contains exceedingly limited reports on chromosome 10p15.3 microdeletions. In the present study, two cases of fetuses with pure terminal 10p15.3 microdeletion syndrome in a Chinese population were examined, with the objective of enhancing understanding of the genotype-phenotype correlation associated with 10p15.3 microdeletions. METHODS: Two fetuses with chromosome 10p15.3 microdeletion were identified from a cohort of 5,258 cases undergoing amniocentesis. Karyotyping and chromosomal microarray analysis (CMA) was conducted to assess chromosomal abnormalities and detect copy number variations (CNVs) within the families, respectively. RESULTS: In Family 1, the fetus exhibited a 556.2-Kb deletion in the 10p15.3 region, encompassing OMIM genes such as DIP2C and ZMYND11, and presented with increased nuchal translucency on prenatal ultrasound examination. Parental CMA analysis revealed that the 10p15.3 microdeletion was inherited from the father, who displayed mild language impairment. In Family 2, a comparable 10p15.3 microdeletion was identified in a fetus presenting with asymmetric butterfly vertebrae at T10 and T12, along with mild scoliosis of the spine. Family 1 elected to terminate the pregnancy, while Family 2 chose to continue. At a follow-up conducted at one year and eight months, the child demonstrated delays in both speech and motor development. CONCLUSION: The present study is the first to report two cases of pure terminal chromosome 10p15.3 microdeletion syndrome in fetuses, offering valuable insights for the prenatal diagnosis of 10p15.3 microdeletion syndrome. Further, it is the first to describe mild clinical features, specifically limited to language impairment, in a patient with 10p15.3 microdeletion syndrome.

Female↗

PubMed2026

Prenatal Phenotypic Features of Five Fetal Cases With RNU4ATAC-Associated Microcephalic Osteodysplastic Primordial Dwarfism Type I.

OBJECTIVE: To present the prenatal sonographic features, genomic findings, and pregnancy outcomes of fetuses with biallelic pathogenic RNU4ATAC variants linked to microcephalic osteodysplastic primordial dwarfism type I (MOPD1). METHODS: This retrospective case series includes five prenatal cases with MOPD1. Diagnoses were established by prenatal ultrasound and genetic testing. Genome sequencing (GS) or targeted exome sequencing (ES) detected the variants either prenatally or after termination of pregnancy (TOP). Clinical data including parental demographics, ultrasound findings, and pregnancy outcomes were collected. RESULTS: All fetuses presented with consistent anomalies on ultrasound including intrauterine growth restriction (IUGR), microcephaly, agenesis of the corpus callosum (ACC), intracranial cysts, lissencephaly, and micrognathia. IUGR was the earliest anomaly detected in all five cases. Prenatal ultrasound findings suggestive of skeletal dysplasia were identified in one case. All cases carried biallelic pathogenic RNU4ATAC variants associated with MOPD1. TOP was chosen in four cases. One fetus was delivered at 39 + 1 weeks with genetic diagnosis confirmed at 27 weeks. CONCLUSION: IUGR, microcephaly and ACC can be detected in fetuses with MOPD1 at around 18 weeks of gestation. Interestingly, skeletal dysplasia was not a consistent prenatal finding. Variants in the non-coding RNU4ATAC gene need to be detected by GS or targeted approaches beyond standard ES.

Humans↗

PubMed2026

Prevalence, species diversity, and antimicrobial resistance profiles of Campylobacter spp. among children under five years of age with acute diarrhea in Ouagadougou, Burkina Faso.

Campylobacter species are major causes of pediatric gastroenteritis worldwide, yet their burden remains underestimated in West Africa due to diagnostic challenges. This study aimed to determine the prevalence, species diversity, and antimicrobial resistance (AMR) profiles of Campylobacter spp. among children under 5 years of age with acute diarrhea in Ouagadougou, Burkina Faso. From 1 May 2023 to 30 April 2024, 383 stool samples were collected at the Centre Hospitalier Universitaire Pédiatrique Charles de Gaulle. Samples were analyzed using standard culture on Karmali selective agar and biochemical identification via the API Campy system. AMR testing was performed using the disk diffusion method. Campylobacter spp. were detected in 33 samples (8.6% prevalence). Infection was significantly associated with the 12-23 months age group (48.5%; P < 0.05). Campylobacter jejuni was the most common species (42.4%), followed by C. coli (21.2%) and C. fetus subsp. fetus (21.2%). Other species included C. hyointestinalis (6.1%), C. sputorum (6.1%), and C. lari (3.0%). Alarmingly, 100% of isolates were resistant to ampicillin, erythromycin, and tetracycline. High resistance rates were also observed for amoxicillin-clavulanic acid (93.9%) and ciprofloxacin (75.8%). Gentamicin showed the highest susceptibility (57.6%). All isolates (100%) were classified as multidrug-resistant (MDR). These results highlight a high prevalence of MDR Campylobacter in Ouagadougou, with total resistance to erythromycin, the first-line treatment. The identification of C. fetus at 42°C suggests a high environmental and zoonotic pressure. These findings underscore the urgent need for enhanced genomic surveillance and updated clinical management guidelines for pediatric diarrhea in the region.IMPORTANCEThis study highlights the burden and antimicrobial resistance of Campylobacter spp. among children under five with acute diarrhea in Burkina Faso. Culture-based detection identified Campylobacter in 8.6% of children, confirming its role as an important but under-recognized cause of pediatric diarrheal disease. High levels of antimicrobial resistance, including complete resistance to erythromycin, raise concerns about the effectiveness of commonly used treatment options. The identification of multiple Campylobacter species, including C. fetus, suggests a broader diversity of circulating strains and possible zoonotic transmission pathways. These findings provide valuable baseline data to strengthen antimicrobial resistance surveillance, improve diagnostic practices, and support evidence-based treatment strategies in West African settings.

Humans↗

PubMed2026

Phenotypes of Hereditary Diseases Associated With Rauch-Steindl Syndrome.

PURPOSE: Prenatal phenotypic manifestations of genetic disorders associated with NSD2 variants remain poorly characterized. This study presents our institutional experience with the prenatal diagnosis of NSD2-associated genetic disorders, specifically Rauch-Steindl syndrome (RAUST), aiming to improve understanding of both the molecular and clinical features of RAUST. METHODS: We performed a retrospective analysis of six fetuses and one adult diagnosed with RAUST at our institution and thoroughly reviewed the prenatal ultrasound reports of six fetuses. Prenatal and postnatal phenotypes of RAUST cases were summarized alongside findings from previously published literature. Correlations between NSD2 variant locations, variant types, and phenotypes were analyzed. Additionally, protein modeling was used to visualize structural changes in NSD2 protein before and after C-terminal variants. We integrated single-cell transcriptomic and gene expression data from multiple public databases to investigate spatiotemporal expression patterns of NSD2 during human fetal development. RESULTS: Fetal growth restriction (FGR) was the most prevalent prenatal manifestation in RAUST fetuses, followed by microcephaly. Bilateral renal hypoplasia emerged as a novel prenatal ultrasonographic feature. Postnatally, speech and motor developmental delays were the most commonly reported phenotypes, followed by physical developmental delays and intellectual disability. Genotype-phenotype correlation analysis revealed an association between N-terminal truncating variants in NSD2 and impaired fetal growth parameters. Notably, C-terminal truncating variants-predicted not to directly impact NSD2 functional domains-also exerted disease-causing effects. CONCLUSION: This study provides a comprehensive analysis of prenatal phenotypes in RAUST cases, enriching the prenatal phenotypic spectrum of the disease and facilitating early diagnosis and clinical management of RAUST. Furthermore, our genotype-phenotype correlation findings lay a foundational basis for future research into the complex molecular mechanisms underlying NSD2-associated genetic disorders.

Humans↗

PubMed2026

Is There Potential Clinical Utility in Reporting Variants of Uncertain Significance From Prenatal Sequencing?

OBJECTIVE: Prenatal sequencing of fetuses with abnormalities detected on imaging is expanding globally. Debate continues over whether variants of uncertain significance (VUS) should be reported prenatally, with some recent national position statements opposing this. In England, VUS that fit the fetal phenotype and require little further evidence for upgrade are discussed at multidisciplinary team (MDT) meetings to determine whether to report. We review the VUS reported by one English laboratory that provides prenatal sequencing to half of England. METHOD: The laboratory's database was searched from 01/10/2020 to 30/04/2025 to ascertain all cases where a VUS was reported. Pregnancy outcomes were obtained from local clinical teams to determine whether the VUS status had been resolved. RESULTS: VUS were reported in 41/881 fetuses sequenced. Follow-up data were available for 38/41 cases, of which 23 were subsequently upgraded to likely pathogenic and 1 downgraded to likely benign. The most common reason for upgrade was new information from post-mortem or postnatal review (17/23). CONCLUSION: There is clinical utility in reporting VUS from prenatal sequencing following MDT discussion. Although reporting VUS leaves parents with uncertainty, follow up (including post-mortem when applicable) resolves this in over 50% of cases (79% of cases re-examined pre- or postnatally).

Humans↗

PubMed2026

Prenatal diagnosis of glucose-6-phosphatase catalytic subunit 3 deficiency (Dursun syndrome) using whole-exome sequencing: A case report of severe fetal cardiomyopathy in a consanguineous family.

Glucose-6-phosphatase catalytic subunit 3 deficiency, also known as Dursun syndrome, is a rare autosomal recessive disorder characterized by severe congenital neutropenia and variable multisystem malformations, particularly affecting the cardiovascular system. Most reported cases have been identified postnatally, following infectious or hematologic complications. Prenatal identification remains exceptionally rare. We describe the case of a fetus from consanguineous parents with a history of multiple neonatal deaths. Serial prenatal imaging demonstrated progressive fetal growth restriction, cardiomegaly with biventricular hypertrophy, significant tricuspid regurgitation, right-sided cardiac dominance, right atrial enlargement, ventriculomegaly, and evolving craniofacial dysmorphism. Whole-exome sequencing revealed a homozygous nonsense variant in G6PC3 (NM_138387.3:c.481C > T; p.(Arg161Ter)), confirming that both parents were heterozygous carriers. Postnatally, the neonate developed severe neutropenia, complex right-sided cardiac outflow obstruction physiology, and refractory cardiorespiratory failure, leading to death on day 4 of life. This report expands the prenatal phenotypic spectrum of glucose-6-phosphatase catalytic subunit 3 deficiency and emphasizes the importance of considering this diagnosis in fetuses presenting with cardiomyopathy, dysmorphic features, fetal growth restriction, and parental consanguinity. Early molecular diagnosis enables accurate counseling, informed reproductive planning, and consideration of preconception or early prenatal genomic testing in high-risk families.

Humans↗

PubMed2025

Antenatal phenotype associated with PAK2 pathogenic variants: bilateral pleural effusion as a warning sign.

Fetal pleural effusions can arise in various contexts with different prognosis. They have been reported in fetuses presenting with hereditary or acquired conditions. One particularly rare genetic disorder, known as Knobloch syndrome, seems to emerge as a potential new cause of fetal pleural effusions, associated with severe outcomes. Knobloch syndrome 1 can be caused by biallelic variants in COL18A1. It is primarily characterized by its ophthalmic features, including severe vitreoretinal degeneration with retinal detachment and macular abnormalities. Neurological defects such as encephalocele and developmental delay, along with skeletal and renal malformations, are also associated with the syndrome. The Knobloch syndrome 2 is caused by monoallelic variants in the kinase domain of PAK2. It is less described and seems to also be associated with cardiac and respiratory damage in addition to the Knobloch syndrome 1 phenotype. PAK2 is a ubiquitous protein with a major implication in regulation and remodeling of the cytoskeleton and numerous other cellular pathways. Knobloch-associated variants seem to cause a loss of the kinase function of the protein. Even if the ophthalmic defects are almost constant, PAK2-associated Knobloch syndrome has slightly different features from Knobloch syndrome 1 in which pulmonary and lymphatic damages are still unseen. In a prenatal trio exome sequencing, we identified a novel de novo PAK2 missense variant, NM_002577.4:c.836 A > C, p.(Gln279Pro), classified as likely pathogenic in a 24 weeks of gestation fetus whose only sign was severe bilateral pleural effusion. From a literature review of patients, we recognize this sign as an important antenatal indicator of Knobloch syndrome 2, as it was the first sign identifiable in 2 out of 5 patients. This adds new evidence for the implication of this gene in fetal pleural effusions, with potentially severe outcomes.

Female↗