ArticleNeurogenetics2018
A novel missense variant in the SDR domain of the WWOX gene leads to complete loss of WWOX protein with early-onset epileptic encephalopathy and severe developmental delay.
Article in Neurogenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene.Molecular genetics & genomic medicine · 2024Article
- Case report: Adult patient withFrontiers in genetics · 2024Article
- Population genetics of marmosets in Asian primate research centers and loci associated with epileptic risk revealed by whole-genome sequencing.Zoological research · 2023Article
- WWOX developmental and epileptic encephalopathy: Understanding the epileptology and the mortality risk.Epilepsia · 2023Article
- Neuroimaging features of WOREE syndrome: a mini-review of the literature.Frontiers in pediatrics · 2023Review
- WWOX and metabolic regulation in normal and pathological conditions.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Article
- Zebrafish Models of Autosomal Recessive Ataxias.Cells · 2021Review
- Neurological Disorders Associated with WWOX Germline Mutations-A Comprehensive Overview.Cells · 2021Review
- Associations betweenAging · 2021Article
- Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development.Frontiers in neuroscience · 2020Article
- Loss of Wwox Causes Defective Development of Cerebral Cortex with Hypomyelination in a Rat Model of Lethal Dwarfism with Epilepsy.International journal of molecular sciences · 2019Article
- TheFrontiers in cellular neuroscience · 2019Article
- WWOX-associated encephalopathies: identification of the phenotypic spectrum and the resulting genotype-phenotype correlation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018Article
- Novel Homozygous Mutation in the WWOX Gene Causes Seizures and Global Developmental Delay: Report and Review.Translational neuroscience · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human WWOX (WW domain-containing oxidoreductase) gene, originally known as a tumor suppressor gene, has been shown to be important for brain function and development. In recent years, mutations in WWOX have been associated with a wide phenotypic spectrum of autosomal recessively inherited neurodevelopmental disorders. Whole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. Functional WWOX analysis was performed in fibroblasts of one patient. Transcription and translation were assessed by quantitative real-time PCR and Western blotting. We report two related patients who presented with early epilepsy refractory to treatment, progressive microcephaly, profound developmental delay, and brain MRI abnormalities. Additionally, one of the patients showed bilateral optic atrophy. Whole exome sequencing revealed homozygosity for a novel missense variant affecting the evolutionary conserved amino acid Gln230 in the catalytic short-chain dehydrogenase/reductase (SDR) domain of WWOX in both girls. Functional studies showed normal levels of WWOX transcripts but absence of WWOX protein. To our knowledge, our patients are the first individuals presenting the more severe end of the phenotypic spectrum of WWOX deficiency, although they were only affected by a single missense variant of WWOX. This could be explained by the functional data indicating an impaired translation or premature degradation of the WWOX protein.
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