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Keywords = decreased fetal movements

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9 pages, 1504 KiB  
Case Report
Zigzag Fetal Heart Rate Pattern in an Uncomplicated Pregnancy with Dual Intrauterine Infection Detected During Labor with Intact Membranes: A Case Report
by Martina Derme, Valentina Demarco, Adele Vasta, Paola Galoppi, Ilenia Mappa and Giuseppe Rizzo
Healthcare 2025, 13(14), 1726; https://doi.org/10.3390/healthcare13141726 - 17 Jul 2025
Viewed by 292
Abstract
Background: Histologic chorioamnionitis (HCA) is a placental inflammatory condition characterized by neutrophilic infiltration of the fetal membranes, often occurring without overt clinical signs or symptoms. Risk factors include prolonged labor, premature rupture of membranes (PROM) exceeding 12 h, nulliparity, labor dystocia, and [...] Read more.
Background: Histologic chorioamnionitis (HCA) is a placental inflammatory condition characterized by neutrophilic infiltration of the fetal membranes, often occurring without overt clinical signs or symptoms. Risk factors include prolonged labor, premature rupture of membranes (PROM) exceeding 12 h, nulliparity, labor dystocia, and lower socioeconomic status. Although HCA frequently presents as a subclinical condition, its early diagnosis remains challenging. Nevertheless, HCA is associated with an increased risk of maternal and neonatal morbidity, including early-onset neonatal sepsis, cerebral palsy, and long-term neurodevelopmental impairment. We report the case of a 29-year-old primigravida at 40 + 0 weeks of gestation, admitted for decreased fetal movements. Discussion: Cardiotocographic (CTG) monitoring revealed a “zigzag pattern” in the absence of maternal fever, leukocytosis, or tachycardia. Due to the CTG findings suggestive of possible fetal compromise, in addition to reduced fetal movements, an emergency cesarean section was performed. Intraoperative findings included heavily meconium-stained amniotic fluid, then the examination of the placenta confirmed acute HCA with a maternal inflammatory response, without evidence of fetal inflammatory response. Conclusion: This case highlights the crucial role of CTG abnormalities, particularly the “zigzag pattern,” as an early marker of subclinical intrauterine inflammation. Early recognition of such patterns may facilitate timely intervention and improve perinatal outcomes in cases of histologic chorioamnionitis. Full article
(This article belongs to the Section Women's Health Care)
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18 pages, 4486 KiB  
Article
Ibuprofen Does Not Prevent Inhibition of Fetal Breathing Movements Caused by Intrauterine Inflammation in Fetal Sheep
by Nhi T. Tran, Vanesa Stojanovska, Sharmony B. Kelly, Kayla Vidinopoulos, John Atta, Eva Matthews-Staindl, Valerie A. Zahra, Yen Pham, Eric A. P. Herlenius, Stuart B. Hooper, Beth J. Allison, Robert Galinsky and Graeme R. Polglase
Int. J. Mol. Sci. 2025, 26(12), 5591; https://doi.org/10.3390/ijms26125591 - 11 Jun 2025
Viewed by 435
Abstract
Antenatal inflammation/infection is a major cause of neonatal apnoea and hypoventilation. Prostaglandin E2 (PGE2) is a key inflammatory mediator associated with depression of fetal and neonatal breathing. We aimed to determine whether antenatal ibuprofen, a cyclooxygenase inhibitor that reduces synthesis of [...] Read more.
Antenatal inflammation/infection is a major cause of neonatal apnoea and hypoventilation. Prostaglandin E2 (PGE2) is a key inflammatory mediator associated with depression of fetal and neonatal breathing. We aimed to determine whether antenatal ibuprofen, a cyclooxygenase inhibitor that reduces synthesis of PGE2, restores fetal breathing movements (FBM) in late-gestation fetal sheep exposed to systemic lipopolysaccharide (LPS). Fetal sheep (125 days gestation, d; term ~148 d) were instrumentally monitored for continuous measurement of FBM and physiological parameters. At 130 d fetuses were randomly allocated between groups receiving i.v. saline (CTLSAL, n = 9), escalating doses of LPS (i.v.) over 3 days (LPSSAL, n = 8), or ibuprofen one hour after each LPS dose (LPSIBU, n = 8). Regular plasma samples were collected for PGE2 assessment. At 135 d, cerebrospinal fluid and brainstem tissue were collected at autopsy for assessments of PGE2 expression, and immunohistochemical quantification of astrocytes and microglia within key brainstem respiratory centres was performed to assess inflammation. LPS exposure increased PGE2 levels in plasma, cerebrospinal fluid and the RTN/pFRG (p < 0.05) and decreased the incidence, amplitude and amount of the accentuated (>5 mmHg) FBMs. Ibuprofen reduced plasma and RTN/pFRG PGE2 expression (p < 0.01 and p = 0.031, respectively) but did not restore FBMs. Astrocyte and microglial density increased in the RTN/pFRG, NTS and raphe nucleus in LPSIBU fetuses, compared to LPSSAL (p < 0.05). Antenatal ibuprofen treatment did not restore depressed FBM, despite reducing the circulating and brainstem PGE2 levels in LPS-exposed fetal sheep. Other inflammatory pathways or more specific targeting of PGE2 may be more effective in preventing apnoea caused by exposure to intrauterine infection/inflammation. Full article
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5 pages, 4993 KiB  
Case Report
Successful Delayed Interval Delivery in Twin Pregnancy After Early Premature Rupture of Membranes of a Leading Fetus: A Case Report
by Won-Kyu Jang
Medicina 2024, 60(11), 1800; https://doi.org/10.3390/medicina60111800 - 2 Nov 2024
Viewed by 1746
Abstract
A 36-year-old primigravida conceived dichorionic diamniotic twins via in vitro fertilization. The first twin experienced premature rupture of membranes at 18 weeks and 5 days of gestation. Despite antibiotic treatment, the first fetus suffered intrauterine fetal death and was delivered three days later [...] Read more.
A 36-year-old primigravida conceived dichorionic diamniotic twins via in vitro fertilization. The first twin experienced premature rupture of membranes at 18 weeks and 5 days of gestation. Despite antibiotic treatment, the first fetus suffered intrauterine fetal death and was delivered three days later at 19 weeks and 1 day. Using ritodrine, the remaining umbilical cord was repositioned, and an emergency cerclage was performed. Ritodrine was continuously administered post-surgery but discontinued at 24 weeks and 3 days due to improved uterine contractions. The patient later delivered a healthy baby via cesarean section at 38 weeks due to decreased fetal movement and breech presentation. This rare case of premature rupture of membranes in one of the twins before the viability term, followed by a successful delayed delivery, is presented here. Full article
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19 pages, 1568 KiB  
Systematic Review
Maternal Fever and Reduced Fetal Movement as Predictive Risk Factors for Adverse Neonatal Outcome in Cases of Congenital SARS-CoV-2 Infection: A Meta-Analysis of Individual Participant Data from Case Reports and Case Series
by Elena S. Bernad, Florentina Duica, Panagiotis Antoniadis, Andreea Moza, Diana Lungeanu, Marius Craina, Brenda C. Bernad, Edida Maghet, Ingrid-Andrada Vasilache, Anca Laura Maghiari, Diana-Aurora Arnautu and Daniela Iacob
Viruses 2023, 15(7), 1615; https://doi.org/10.3390/v15071615 - 24 Jul 2023
Cited by 3 | Viewed by 3719
Abstract
Objectives: To determine risk factors for primary and secondary adverse neonatal outcomes in newborns with congenital SARS-CoV-2 infection. Data sources: PubMed/MEDLINE and Google Scholar from January 2020 to January 2022. Study eligibility criteria: newborns delivered after 24 weeks of gestation with confirmed/possible congenital [...] Read more.
Objectives: To determine risk factors for primary and secondary adverse neonatal outcomes in newborns with congenital SARS-CoV-2 infection. Data sources: PubMed/MEDLINE and Google Scholar from January 2020 to January 2022. Study eligibility criteria: newborns delivered after 24 weeks of gestation with confirmed/possible congenital SARS-CoV-2 infection, according to standard classification criteria. Methods: Execution of the IPD analyses followed the PRISMA-IPD statement. Univariate non-parametric tests compared numerical data distributions. Fisher’s exact or Chi-square test determined categorical variables’ statistical significance. Multivariate logistic regression revealed risk factors for adverse neonatal outcome. Results: Maternal fever was associated with symptomatic congenital infection (OR: 4.55, 95% CI: 1.33–15.57). Two-thirds of women that reported decreased fetal movements were diagnosed with IUFD (p-value = 0.001). Reduced fetal movement increased the risk of intrauterine fetal death by 7.84 times (p-value = 0.016, 95% CI: 2.23–27.5). The risk of stillbirth decreased with gestational age at the time of maternal infection (p-value < 0.05, OR: 0.87, 95% CI: 0.79–0.97). Conclusions: Maternal fever and perception of reduced fetal movement may be predictive risk factors for adverse pregnancy outcome in cases with congenital SARS-CoV-2 infection. Full article
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10 pages, 762 KiB  
Article
Fetal Movement Counting in Prolonged Pregnancies: The COMPTAMAF Prospective Randomized Trial
by Louise Moniod, Agathe Hovine, Béatrice Trombert, Florence Rancon, Paul Zufferey, Laura Chauveau, Céline Chauleur and Tiphaine Raia-Barjat
Healthcare 2022, 10(12), 2569; https://doi.org/10.3390/healthcare10122569 - 18 Dec 2022
Cited by 2 | Viewed by 2918
Abstract
In prolonged pregnancies, the risks of neonatal morbidity and mortality are increased. The aim of this trial was to assess the benefits of maternal information about fetal movement (FM) counting on neonatal outcomes in prolonged pregnancy. It was a prospective, single center, randomized, [...] Read more.
In prolonged pregnancies, the risks of neonatal morbidity and mortality are increased. The aim of this trial was to assess the benefits of maternal information about fetal movement (FM) counting on neonatal outcomes in prolonged pregnancy. It was a prospective, single center, randomized, open-label study conducted from October 2019 to March 2022. Intention-to-treat analyses were performed on 278 patients randomized into two 1:1 groups (control group and FM counting group). The primary outcome was a composite score of neonatal morbidity (presence of two of the following items: fetal heart rate abnormality at delivery, Apgar score of <7 at 5 min, umbilical cord arterial pH of <7.20, and acute respiratory distress with mutation in neonatal intensive care unit). There was no significant difference between the two groups in the rate of neonatal morbidity (14.0% in the FM counting group versus 22.9% in the standard information group; p = 0.063; OR 0.55, 95% CI 0.29–1.0). In this study, fetal movement counting for women in prolonged pregnancy failed to demonstrate a significant reduction in adverse neonatal outcomes. Full article
(This article belongs to the Special Issue Safety and Quality in Maternal and Neonatal Care)
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12 pages, 1641 KiB  
Article
The Effects of Prenatal Exposure to Pregabalin on the Development of Ventral Midbrain Dopaminergic Neurons
by Walaa F. Alsanie, Majid Alhomrani, Ahmed Gaber, Hamza Habeeballah, Heba A. Alkhatabi, Raed I. Felimban, Sherin Abdelrahman, Charlotte A. E. Hauser, Adeel G. Chaudhary, Abdulhakeem S. Alamri, Bassem M. Raafat, Abdulwahab Alamri, Sirajudheen Anwar, Khaled A. Alswat, Yusuf S. Althobaiti and Yousif A. Asiri
Cells 2022, 11(5), 852; https://doi.org/10.3390/cells11050852 - 1 Mar 2022
Cited by 6 | Viewed by 4990
Abstract
Pregabalin is widely used as a treatment for multiple neurological disorders; however, it has been reported to have the potential for misuse. Due to a lack of safety studies in pregnancy, pregabalin is considered the last treatment option for various neurological diseases, such [...] Read more.
Pregabalin is widely used as a treatment for multiple neurological disorders; however, it has been reported to have the potential for misuse. Due to a lack of safety studies in pregnancy, pregabalin is considered the last treatment option for various neurological diseases, such as neuropathic pain. Therefore, pregabalin abuse in pregnant women, even at therapeutic doses, may impair fetal development. We used primary mouse embryonic neurons to investigate whether exposure to pregabalin can impair the morphogenesis and differentiation of ventral midbrain neurons. This study focused on ventral midbrain dopaminergic neurons, as they are responsible for cognition, movement, and behavior. The results showed that pregabalin exposure during early brain development induced upregulation of the dopaminergic progenitor genes Lmx1a and Nurr1 and the mature dopaminergic gene Pitx3. Interestingly, pregabalin had different effects on the morphogenesis of non-dopaminergic ventral midbrain neurons. Importantly, our findings illustrated that a therapeutic dose of pregabalin (10 μM) did not affect the viability of neurons. However, it caused a decrease in ATP release in ventral midbrain neurons. We demonstrated that exposure to pregabalin during early brain development could interfere with the neurogenesis and morphogenesis of ventral midbrain dopaminergic neurons. These findings are crucial for clinical consideration of the use of pregabalin during pregnancy. Full article
(This article belongs to the Collection Feature Papers in 'Cells of the Nervous System' Section)
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13 pages, 506 KiB  
Article
Prenatal and Neonatal Characteristics of Children with Prader-Willi Syndrome
by Lionne N. Grootjen, Nathalie E. M. Uyl, Inge A. L. P. van Beijsterveldt, Layla Damen, Gerthe F. Kerkhof and Anita C. S. Hokken-Koelega
J. Clin. Med. 2022, 11(3), 679; https://doi.org/10.3390/jcm11030679 - 28 Jan 2022
Cited by 16 | Viewed by 3191
Abstract
Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the [...] Read more.
Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment. Full article
(This article belongs to the Special Issue Endocrinology and Metabolic Diseases: Prader-Willi Syndrome)
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11 pages, 1517 KiB  
Case Report
Decreased Fetal Movements: A Sign of Placental SARS-CoV-2 Infection with Perinatal Brain Injury
by Guillaume Favre, Sara Mazzetti, Carole Gengler, Claire Bertelli, Juliane Schneider, Bernard Laubscher, Romina Capoccia, Fatemeh Pakniyat, Inès Ben Jazia, Béatrice Eggel-Hort, Laurence de Leval, Léo Pomar, Gilbert Greub, David Baud and Eric Giannoni
Viruses 2021, 13(12), 2517; https://doi.org/10.3390/v13122517 - 15 Dec 2021
Cited by 32 | Viewed by 4636
Abstract
Neonatal COVID-19 is rare and mainly results from postnatal transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, can infect the placenta and compromise its function. We present two cases of decreased fetal movements and abnormal fetal heart rhythm 5 days after mild [...] Read more.
Neonatal COVID-19 is rare and mainly results from postnatal transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, can infect the placenta and compromise its function. We present two cases of decreased fetal movements and abnormal fetal heart rhythm 5 days after mild maternal COVID-19, requiring emergency caesarean section at 29 + 3 and 32 + 1 weeks of gestation, and leading to brain injury. Placental examination revealed extensive and multifocal chronic intervillositis, with intense cytoplasmic positivity for SARS-CoV-2 spike antibody and SARS-CoV-2 detection by RT-qPCR. Vertical transmission was confirmed in one case, and both neonates developed extensive cystic peri-ventricular leukomalacia. Full article
(This article belongs to the Special Issue Emerging Virus Infections in Adverse Pregnancy Outcomes)
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9 pages, 1375 KiB  
Article
Kinematic Comparison on Lower Limb Kicking Action of Fetuses in Different Gestational Weeks: A Pilot Study
by Hairong Chen, Yang Song, Rongrong Xuan, Qiuli Hu, Julien S. Baker and Yaodong Gu
Healthcare 2021, 9(8), 1057; https://doi.org/10.3390/healthcare9081057 - 18 Aug 2021
Cited by 5 | Viewed by 2255
Abstract
The fetal movements during different gestational weeks are essential for normal musculoskeletal development. The kinematic characteristics of fetuses with small differences in gestational weeks may be different and important. Ultrasonographic videos of fetal kicking action and plantarflexion action were collected from three healthy [...] Read more.
The fetal movements during different gestational weeks are essential for normal musculoskeletal development. The kinematic characteristics of fetuses with small differences in gestational weeks may be different and important. Ultrasonographic videos of fetal kicking action and plantarflexion action were collected from three healthy pregnant women (24, 27, and 30 gestational weeks) with normal fetal development. The kinematic characteristics, including angular range and angular velocity, were analyzed. These kinematic parameters were measured using simi motion. The final knee angle was found to decrease with progressive gestational weeks. Compared with 24 w, the knee joint angle at 27 w and 30 w was significantly reduced at the end of a kick-type movement (p < 0.01). Except for the mean angular velocity of the knee joint, there were no significant differences in the other conditions. The value at 30 w for mean angular velocity was significantly higher than that at 24 w (p = 0.02). In the ankle joint, no significant differences were observed between different conditions. Therefore, we can conclude that there was no significant difference in the kinematic characteristics of the ankle joint for small gestational age gaps, but there was a significant difference in the knee joint. As the gestation weeks increase, the range of kicking motion tends to decrease. The reason may be that with the increase of gestational weeks, fetal lower limb musculoskeletal development is gradually enhanced; the slower growth rate indicates that development reaches a peak level in weeks 24 to 30. Full article
(This article belongs to the Special Issue Comprehensive Clinical Physiotherapy and Rehabilitation: Version II)
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13 pages, 2860 KiB  
Article
Novel Phonography-Based Measurement for Fetal Breathing Movement in the Third Trimester
by Márton Áron Goda, Tamás Telek and Ferenc Kovács
Sensors 2021, 21(1), 211; https://doi.org/10.3390/s21010211 - 31 Dec 2020
Cited by 5 | Viewed by 3968
Abstract
The detailed assessment of fetal breathing movement (FBM) monitoring can be a pre-indicator of many critical cases in the third trimester of pregnancy. Standard 3D ultrasound monitoring is time-consuming for FBM detection. Therefore, this type of measurement is not common. The main goal [...] Read more.
The detailed assessment of fetal breathing movement (FBM) monitoring can be a pre-indicator of many critical cases in the third trimester of pregnancy. Standard 3D ultrasound monitoring is time-consuming for FBM detection. Therefore, this type of measurement is not common. The main goal of this research is to provide a comprehensive image about FBMs, which can also have potential for application in telemedicine. Fifty pregnancies were examined by phonography, and nearly 9000 FBMs were identified. In the case of male and female fetuses, 4740 and 3100 FBM episodes were detected, respectively. The measurements proved that FBMs are well detectable in the 20–30 Hz frequency band. For these episodes, an average duration of 1.008 ± 0.13 s (p < 0.03) was measured in the third trimester. The recorded material lasted for 16 h altogether. Based on these measurements, an accurate assessment of FBMs could be performed. The epochs can be divided into smaller-episode groups separated by shorter breaks. During the pregnancy, the rate of these breaks continuously decreases, and episode groups become more contiguous. However, there are significant differences between male and female fetuses. The proportion of the episodes which were classified into minimally 10-member episode groups was 19.7% for males and only 12.1% for females, even at the end of the third trimester. In terms of FBM detection, phonography offers a novel opportunity for long-term monitoring. Combined with cardiac diagnostic methods, it can be used for fetal activity assessment in the third trimester and make measurement appreciably easier than before. Full article
(This article belongs to the Special Issue Neurophysiological Monitoring)
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24 pages, 484 KiB  
Review
Maternal Coronavirus Infections and Neonates Born to Mothers with SARS-CoV-2: A Systematic Review
by Waldemar Naves do Amaral, Carolina Leão de Moraes, Ana Paula dos Santos Rodrigues, Matias Noll, Jalsi Tacon Arruda and Carolina Rodrigues Mendonça
Healthcare 2020, 8(4), 511; https://doi.org/10.3390/healthcare8040511 - 24 Nov 2020
Cited by 47 | Viewed by 7290
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is continuously affecting the lives of all people. Understanding the impact of COVID-19 on pregnancy in terms of morbidity, mortality, and perinatal maternal and fetal outcomes is essential to propose strategies for prevention and infection control. Here, [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic is continuously affecting the lives of all people. Understanding the impact of COVID-19 on pregnancy in terms of morbidity, mortality, and perinatal maternal and fetal outcomes is essential to propose strategies for prevention and infection control. Here, we conducted a systematic review to investigate pregnant women infected with COVID-19 in terms of signs and symptoms, type of delivery, comorbidities, maternal and neonatal outcomes, and the possibility of vertical transmission. A search on Embase and PubMed databases was performed on 31 October 2020. Observational studies and case reports on pregnant women infected with COVID-19 were included without language restrictions. The 70 selected studies included a total of 1457 pregnant women diagnosed with COVID-19 in the first, second, and third trimesters of pregnancy. The most common signs and symptoms were fever, cough, and nausea. The most frequent comorbidities were obesity, hypertensive disorders, and gestational diabetes. Among maternal and fetal outcomes, premature birth (n = 64), maternal death (n = 15), intrauterine fetal death or neonatal death (n = 16), cases of intrauterine fetal distress (n = 28), miscarriage (n = 7), decreased fetal movements (n = 19), and severe neonatal asphyxia (n = 5) were the most frequent. Thirty-nine newborns tested positive for SARS-CoV-2. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in the placenta (n = 13) and breast milk (n = 6). This review indicates that COVID-19 during pregnancy can result in maternal, fetal, and neonatal complications. In addition, SARS-CoV-2 viral exposure of neonates during pregnancy and delivery cannot be ruled out. Thus, we highlight the need for long-term follow-up of newborns from mothers diagnosed with COVID-19 to establish the full implications of SARS-CoV-2 infection in these children. Full article
(This article belongs to the Collection COVID-19: Impact on Public Health and Healthcare)
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25 pages, 4020 KiB  
Article
PGAP3 Associated with Hyperphosphatasia with Mental Retardation Plays a Novel Role in Brain Morphogenesis and Neuronal Wiring at Early Development
by Sahar I. Da’as, Waleed Aamer, Waseem Hasan, Aljazi Al-Maraghi, Alya Al-Kurbi, Houda Kilani, Jehan AlRayahi, Khaled Zamel, Mitchell A. Stotland and Khalid A. Fakhro
Cells 2020, 9(8), 1782; https://doi.org/10.3390/cells9081782 - 27 Jul 2020
Cited by 21 | Viewed by 6288
Abstract
Recessive mutations in Post-GPI attachment to proteins 3 (PGAP3) cause the rare neurological disorder hyperphosphatasia with mental retardation syndrome 4 type (HPMRS4). Here, we report a novel homozygous nonsense mutation in PGAP3 (c.265C>T-p.Gln89*), in a 3-year-old boy with unique novel clinical [...] Read more.
Recessive mutations in Post-GPI attachment to proteins 3 (PGAP3) cause the rare neurological disorder hyperphosphatasia with mental retardation syndrome 4 type (HPMRS4). Here, we report a novel homozygous nonsense mutation in PGAP3 (c.265C>T-p.Gln89*), in a 3-year-old boy with unique novel clinical features. These include decreased intrauterine fetal movements, dysgenesis of the corpus callosum, olfactory bulb agenesis, dysmorphic features, cleft palate, left ear constriction, global developmental delay, and hypotonia. The zebrafish functional modeling of PGAP3 loss resulted in HPMRS4-like features, including structural brain abnormalities, dysmorphic cranial and facial features, hypotonia, and seizure-like behavior. Remarkably, morphants displayed defective neural tube formation during the early stages of nervous system development, affecting brain morphogenesis. The significant aberrant midbrain and hindbrain formation demonstrated by separation of the left and right tectal ventricles, defects in the cerebellar corpus, and caudal hindbrain formation disrupted oligodendrocytes expression leading to shorter motor neurons axons. Assessment of zebrafish neuromuscular responses revealed epileptic-like movements at early development, followed by seizure-like behavior, loss of touch response, and hypotonia, mimicking the clinical phenotype human patients. Altogether, we report a novel pathogenic PGAP3 variant associated with unique phenotypic hallmarks, which may be related to the gene’s novel role in brain morphogenesis and neuronal wiring. Full article
(This article belongs to the Special Issue Signaling Pathway Analysis and Disease Modeling in Zebrafish)
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