Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals

Ricci, Emilia; Fetta, Anna; Garavelli, Livia; Caraffi, Stefano Giuseppe; Ivanovski, Ivan; Bonanni, Paolo; Accorsi, Patrizia; Giordano, Lucio; Pantaleoni, Chiara; Romeo, Antonino; Arena, Alessia; Bonetti, S.; Boni, Antonella; Chiarello, Daniela; Pisa, Veronica Di; Epifanio, Roberta; Faravelli, Francesca; Finardi, Erica; Fiumara, Agata; Grioni, Daniele; Mammi, Isabella; Negrin, Susanna; Osanni, Elisa; Raviglione, Federico; Rivieri, Francesca; Rizzi, Romana; Savasta, Salvatore; Tarani, Luigi; Zanotta, Nicoletta; Dormi, Ada; Canevini, Mariapaola; Cordelli, Duccio Maria

doi:10.1016/j.yebeh.2021.108315

Cited by 7 publications

(11 citation statements)

References 35 publications

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“…These options keep in mind the molecular and cellular consequences (e.g., gene expression profiles, cell differentiation states) of Zeb2 deficiency in these mouse models (for a recent review of most mouse models, see [ 30 ]). In addition, we considered deficiencies (with a focus on neurodevelopmental defects) in MOWS patients as documented by clinicians [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. The realistic options in trying to correlate Zeb2 ChIP-seq and Zeb2-perturbation RNA-seq data with MOWS in the clinic are presently three-fold.…”

Section: Resultsmentioning

confidence: 99%

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Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome

Birkhoff

Korporaal

Brouwer

et al. 2023

Genes

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Functional perturbation and action mechanism studies have shown that the transcription factor Zeb2 controls cell fate decisions, differentiation, and/or maturation in multiple cell lineages in embryos and after birth. In cultured embryonic stem cells (ESCs), Zeb2’s mRNA/protein upregulation is necessary for the exit from primed pluripotency and for entering general and neural differentiation. We edited mouse ESCs to produce Flag-V5 epitope-tagged Zeb2 protein from one endogenous allele. Using chromatin immunoprecipitation coupled with sequencing (ChIP-seq), we mapped 2432 DNA-binding sites for this tagged Zeb2 in ESC-derived neuroprogenitor cells (NPCs). A new, major binding site maps promoter-proximal to Zeb2 itself. The homozygous deletion of this site demonstrates that autoregulation of Zeb2 is necessary to elicit the appropriate Zeb2-dependent effects in ESC-to-NPC differentiation. We have also cross-referenced all the mapped Zeb2 binding sites with previously obtained transcriptome data from Zeb2 perturbations in ESC-derived NPCs, GABAergic interneurons from the ventral forebrain of mouse embryos, and stem/progenitor cells from the post-natal ventricular-subventricular zone (V-SVZ) in mouse forebrain, respectively. Despite the different characteristics of each of these neurogenic systems, we found interesting target gene overlaps. In addition, our study also contributes to explaining developmental disorders, including Mowat-Wilson syndrome caused by ZEB2 deficiency, and also other monogenic syndromes.

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Section: Resultsmentioning

confidence: 99%

“…Recent reports have described malformations in the central nervous system of MOWS patients over a broad age range, including defects of the corpus callosum and/or hippocampus, and can be seen by neuroimaging. These reports also followed up on electro-clinical defects, such as focal seizures, with MOWS patients [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome

Birkhoff

Korporaal

Brouwer

et al. 2023

Genes

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“…Given the diverse range of defects associated with MWS, patients suspected of the condition require targeted tests and comprehensive care involving collaboration between multiple specialists. Even though ocular symptoms were observed in only approximately 10% of MWS cases reviewed in the published studies, certain visual disorders, such as congenital cataracts, have the potential to result in irreversible blindness if not promptly treated (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) . Therefore, following a diagnosis of MWS, the child should be referred for an ophthalmological examination to rule out visual disorders.…”

Section: Discussionmentioning

confidence: 99%

Ocular abnormalities in Mowat–Wilson syndrome – a case series of four patients

Bator,

Machaj,

Matus

et al. 2023

Pediatr Med Rodz

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Mowat–Wilson syndrome is a rare genetic disorder. Patients present with characteristic facial dysmorphia, intellectual disability, and disorders of the nervous, circulatory, gastrointestinal, and genitourinary systems. However, in the available literature there are few descriptions of ocular abnormalities, which are a significant problem among children diagnosed with Mowat–Wilson syndrome. This article reports four clinical cases, focusing mainly on the ocular abnormalities that occur during the course of the disease. Even though ophthalmic manifestations, based on the current data, affect less than 10% of patients, if Mowat–Wilson syndrome is suspected or diagnosed, the child should be referred to a medical centre with the highest level of referral for full diagnostics and implementation of specialised treatment.

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“…These larger cohorts lead to a much better genotype–phenotype characterization of these syndromes. In the past 2 years, several single-center and multicentric studies have generated new insights into the electrographic and phenotypic spectrum of the following genetic epilepsies: PIGS-associated early-onset developmental and epileptic encephalopathy [6], Angelman syndrome [7], LAMA-2 -related muscular dystrophy [8], Mowat–Wilson syndrome [9], neurofibromatosis type 1 [10], CLCN4 -related epilepsy [11], Poirier–Bienvenu syndrome [12], and familial cortical myoclonic tremor with epilepsy type 1 [13].…”

Section: Genotype–phenotype Correlationmentioning

confidence: 99%

Updates on the diagnostic evaluation, genotype–phenotype correlation, and treatments of genetic epilepsies

Zimmern

Korff

2022

Current Opinion in Pediatrics

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Purpose of reviewThis article reviews the latest publications in genetic epilepsies, with an eye on publications that have had a translational impact. This review is both timely and relevant as translational discoveries in genetic epilepsies are becoming so frequent that it is difficult for the general pediatrician and even the general child neurologist to keep up.Recent findingsWe divide these publications from 2021 and 2022 into three categories: diagnostic testing, genotype–phenotype correlation, and therapies. We also summarize ongoing and upcoming clinical trials.SummaryTwo meta-analyses and systematic reviews suggest that exome and genome sequencing offer higher diagnostic yield than gene panels. Genotype–phenotype correlation studies continue to increase our knowledge of the clinical evolution of genetic epilepsy syndromes, particularly with regards to sudden death, auditory dysfunction, neonatal presentation, and magnetoencephalographic manifestations. Pyridoxine supplementation may be helpful in seizure management for various genetic epilepsies. There has been interest in using the neurosteroid ganaxolone for various genetic epilepsy syndromes, with clear efficacy in certain trials. Triheptanoin for epilepsy secondary to glucose transporter 1 (GLUT1) deficiency syndrome is not clearly effective but further studies will be needed.

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Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals

Cited by 7 publications

References 35 publications

Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome

Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome

Ocular abnormalities in Mowat–Wilson syndrome – a case series of four patients

Updates on the diagnostic evaluation, genotype–phenotype correlation, and treatments of genetic epilepsies

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