Communications Biology, Год журнала: 2024, Номер 7(1)
Опубликована: Июль 8, 2024
Abstract Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, heterozygous variants NAV3 gene, which encodes microtubule positive tip protein neuron navigator 3 (NAV3). All affected intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, behavioral issues. In mouse brain, Nav3 is throughout with more prominent signatures postmitotic, excitatory, inhibiting, sensory neurons. When overexpressed HEK293T COS7 cells, impaired ability to stabilize microtubules. Further, knocking-down nav3 zebrafish led severe morphological defects, neuronal growth, impairment, were rescued co-injection of WT mRNA not by transcripts encoding variants. Our findings establish role neurodevelopmental disorders, reveal its involvement morphogenesis, neuromuscular responses.
Язык: Английский
Процитировано
3The MED13L Foundation strategic research plan: a roadmap to the future
Therapeutic Advances in Rare Disease, Год журнала: 2024, Номер 5
Опубликована: Янв. 1, 2024
A strategic research plan (SRP) serves as a compass for the patient advocacy organizations driving therapeutic options their rare disorder. The MED13L Foundation commissioned SRP in 2022 through COMBINEDBrain, consortium of neurodevelopmental disorders, working toward clinical trial readiness. is an objective evaluation literature including and basic science knowledge interwoven with assessment preclinical readiness tools necessary achieving interventions. Clinical conducted review documenting symptoms variant information each individual syndrome. Data collated presented summary, providing any unique genotype–phenotype, applicable. Scientific reviewed same manner, identifying areas opportunity to expand Researchers clinicians responsible growing understanding syndrome are interviewed shared create open collaborative network. Preclinical largely framed Food Drug Administration guidelines development therapeutics from bench bedside. Finally, infrastructure community engagement assessed strengths opportunities elevate bond formed drive patient-centered forward. Completed, this becomes living resource set priorities, share researchers clinicians, provide direction reach organizational goals, therapies affected by
Язык: Английский
Процитировано
3How should antenatal counseling be given to parents in the fetal corpus callosum agenesis?
BMC Pregnancy and Childbirth, Год журнала: 2025, Номер 25(1)
Опубликована: Март 8, 2025
We aimed to review the corpus callosum agenesis (CCA) cases diagnosed and managed in our University contribute literature about this antenatally fetal cranial anomaly by revealing antenatal postnatal outcomes of CCA. This retrospective cross-sectional study examined CCA detected clinic between 2012 2021. Genetic results, accompanying additional anomalies, termination, perinatal mortality rates were also calculated. Neurodevelopmental revealed investigating motor development, cognitive behavioral disorder, speech delay, personal-social backwardness, epilepsy isolated non-isolated period. Data from 30 fetuses evaluated during study. The number is 11 (37.5%) 19 (62.5%), respectively, partial complete 8 (26%) 22 (74%), respectively. Among fetuses, numbers live births, chromosomal mortalities, terminations found be 14 (47%), 3 (10%), 13 (43%), Postnatal evaluation was performed children, normal neurodevelopmental observed 5 (35.7%). All these children group. Additionally, poor outcome 37.5% If fetus, ultrasonographic genetic examination should differentiate While termination option can offered family informing them pregnancy CCA, counseling remains contradictory, more comprehensive prospective studies are needed. retrospectively registered authorized local Ethics Committee Ankara (clinical trial date 06.06.2024/ 1391402).
Язык: Английский
Процитировано
0Analysis of Associated Abnormalities and Outcome Assessment in Malformations of the Corpus Callosum Diagnosed via Fetal
Journal of Clinical Ultrasound, Год журнала: 2025, Номер unknown
Опубликована: Апрель 15, 2025
The study explores corpus callosum malformation (CCM) using comprehensive brain Magnetic Resonance Imaging (MRI) for the assessment of associated malformations and their relation to long-term outcomes. During a 7-year period, all cases CCM diagnosed via fetal MRI were retrospectively studied. Neurodevelopmental outcomes assessed through postnatal interviews. Fetal imaging was performed 1.5-T scanner without sedation, focusing on CC development anomalies. included 59 participants with CCM. Isolated observed in 25.4% cases, while 74.6% presented additional intracranial abnormalities, including cortical (45.8%), periventricular nodular heterotopia (25.4%), supratentorial parenchymal signal intensity abnormality sulcation delay (16.9%). Additionally, 16.9% non-neurological anomalies, such as craniofacial (8.5%) urinary abnormalities (5.1%). In terms pregnancy outcomes, 20.3% underwent termination, 5.1% ended stillbirth, 22.0% resulted death after birth, 52.5% live births. A significant association between coexistence poor prognosis (p = 0. 012). broad spectrum anomalies linked CCM, along clinical underscores pivotal role prenatal screening fetuses
Язык: Английский
Процитировано
0Midline defect with corpus callosum agenesis, vermian hypoplasia and median cleft lip palate
Case Reports in Perinatal Medicine, Год журнала: 2025, Номер 14(1)
Опубликована: Янв. 1, 2025
Abstract Objectives Midline defects in the brain may be related to genetic syndromes. Association with facial anomalies and skeletal deformities has been described. Case presentation In present case, a routine second trimester scan revealed cerebral abnormalities (corpus callosum agenesis, cerebellar cleft due vermian hypoplasia, ventriculomegaly), suspected cortical developmental disorder, hypertelorism, hypoplastic nasal bone, small median lip palate, abnormal profile, as well syndactyly of left hand involving fourth fifth finger. Genetic testing normal karyotype. Subsequent trio exome sequencing did not identify any pathogenic variants or unknown significance. The vaginal delivery at term postnatal adaptation were uneventful. Postnatal neurosonographic imaging clinical evaluation confirmed prenatal findings. Both mother child discharged healthy condition scheduled follow-ups. Differential diagnoses include Hartsfield-Bixler-Demyer Syndrome, Oro-Facial-Digital-Syndromes, Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate Syndrome Acrocallosal Syndrome. Conclusions Invasive diagnostic are recommended when multiple fetal suggest potential syndrome. While all cases reveal an underlying cause, findings can provide valuable information help parents healthcare providers make informed decisions about continuation pregnancy.
Язык: Английский
Процитировано
0Genetic etiology of agenesis of the corpus callosum: a retrospective single-center cohort analysis of 114 fetuses
Archives of Gynecology and Obstetrics, Год журнала: 2024, Номер 310(1), С. 181 - 194
Опубликована: Май 23, 2024
Язык: Английский
Процитировано
2Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up
Children, Год журнала: 2024, Номер 11(7), С. 797 - 797
Опубликована: Июнь 28, 2024
Introduction: The corpus callosum is one of the five main cerebral commissures. It key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). dys- agenesis a rare disease (1:4000 live births), but it have serious mental effects. Methods: In our study, we processed data 64 pregnant women. They attended prenatal diagnostic center genetic counseling from 2005 2019 at Department Obstetrics Gynecology Semmelweis University. Results: pregnancies had following outcomes: 52 ended in delivery, 1 spontaneous abortion, 11 termination pregnancy (TOP) cases (n = 64). average time detection with imaging tests was 25.24 gestational weeks. 16 cases, magnetic resonance (MRI) performed. If abnormality detected before 20th week, test performed on an amniotic fluid sample obtained amniocentesis. Karyotyping cytogenetic were 15 investigated cases. gave normal results three (46,XX XY). these postnatally chromosomal microarray (CMA) later performed, which confirmed Aicardi syndrome (3q21.3–21.1 microdeletion). case, postnatally, found Wiedemann–Rautenstrauch syndrome. other X ring, Di George syndrome, 46,XY,del(13q)(q13q22) 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards diagnosed six Patau case. Conclusions: We that abnormalities are often linked problems. recommend all rule out inherited diseases. Also, long-term outcome does not just depend disease’s severity associated conditions, hence proper follow-up early development also key. For this reason, close teamwork between neonatology, developmental neurology, pediatric surgery vital.
Язык: Английский
Процитировано
2Parental magnetic resonance imaging for the evaluation of fetuses with brain anomalies
Developmental Medicine & Child Neurology, Год журнала: 2024, Номер unknown
Опубликована: Сен. 11, 2024
Abstract Aim To evaluate the role of parental magnetic resonance imaging (MRI) in assessing fetuses with suspected brain anomalies and its use prenatal counselling. Method A retrospective, multicentre chart review was conducted on who underwent MRI because abnormalities between January 2008 December 2022, one or both parents (MRI‐Trio) as part Clinical demographic data were collected, including fetal findings, counselling outcomes, genetic testing results, family previous pregnancy history, neurological examinations born children up to 24 months age, autopsy reports from terminated pregnancies. MRI‐Trio concordance defined at least abnormal feature identified similarity fetus parents. The live‐born assessed postnatally through either neurodevelopmental evaluations telephone interviews. Results Sixty pregnancies included (41.7% concordant 58.3% discordant MRI‐Trio). Forty‐two (70%) 17 (28.3%). One case utero death (1.7%) reported. most common findings multiple ( n = 26, 43.3%), isolated disorders corpus callosum 17, 28.3%), atypical periventricular pseudocysts 6, 10%), anterior complex 4, 6.7%). enabled better prognostication. When concordant, more favourable 22, 36.6%) majority exhibited typical development p < 0.001). Interpretation is a valuable tool for identifying dominantly inherited that may not hold developmental significance are associated acknowledging potential variable penetrance, which result severe presentations. Concordant can enhance accuracy counselling, potentially reducing incidence termination pregnancy.
Язык: Английский
Процитировано
2The High Diagnostic Yield of Prenatal Exome Sequencing Followed by 3400 Gene Panel Analysis in 629 Ongoing Pregnancies With Ultrasound Anomalies
Prenatal Diagnosis, Год журнала: 2024, Номер unknown
Опубликована: Сен. 30, 2024
ABSTRACT Background The aim of this study was to evaluate the diagnostic yield routine exome sequencing (ES) in fetuses with ultrasound anomalies. Methods We performed a retrospective analysis ES results 629 isolated or multiple anomalies referred 2019–2022. Variants gene panel consisting approximately 3400 genes associated congenital and/or intellectual disability were analyzed. used trio and filtering for de novo variants, compound heterozygous homozygous X‐linked variants imprinted genes, known pathogenic variants. Results Pathogenic likely (class five four, respectively) identified 14.0% (88/629, 95% CI 11.5%–16.9%) cases. In current cohort, probability detecting monogenetic disorder ∼1:7 1:8.7–1:5.9), ranging from 1:9 (49/424) cases one major anomaly 1:5 (32/147) system Conclusions Our indicate that notable number (1:7) normal chromosomal microarray have (likely) variant can be detected through prenatal ES. These warrant implementation selected cases, including those an on ultrasound.
Язык: Английский
Процитировано
1Corpus Callosum Malformations
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
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