Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene

• Published in: Molecular genetics & genomic medicine 2024-08, Vol.12 (8), p.e2500-n/a
• Main Authors: You, Yang, Wu, Wenjuan, Du, Yakun, Hu, Jintong, Li, Baoguang
• Format: Article
• Language: English
• Subjects: Age; Anticonvulsants - therapeutic use; Central nervous system; Child development; Chromosomes; Cloning; Convulsions & seizures; developmental epileptic encephalopathy; Electroencephalography; Electromyography; Encephalopathy; Epilepsy; Female; Gene sequencing; Genes; Genetic testing; Homozygosity; Homozygote; Humans; Hypotonia; Infant; Infants; Mutation; Original; Patients; Phenotype; Phenotypes; Phenotypic variations; Plasmids; Proteins; Seizures; Spasms; Spasms, Infantile - genetics; Spasms, Infantile - pathology; Tumor Suppressor Proteins; Ultrasonic imaging; Vigabatrin - therapeutic use; Whole genome sequencing; WW Domain-Containing Oxidoreductase - genetics; WWOX
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2500

Background Variations in the WWOX gene have been identified as the leading cause of several central nervous system disorders. However, most previous reports have focused on the description of clinical phenotype, neglecting functional verification. Herein, we presented a case of a patient with developmental epileptic encephalopathy (DEE) caused by WWOX gene variation. Case Presentation Our patient was a 13‐month‐old girl with abnormal facial features, including facial hypotonia, arched eyebrows, a broad nose, and a depressed nasal bridge. She also had sparse and yellow hair, a low anterior hairline, and a short neck. Before the age of 8 months, she was suffering from mild seizures. Her developmental delay gradually worsened, and she suffered infantile spasms. After treatment with vigabatrin, seizures subsided. WWOX gene homozygous variation c.172+1G>C was identified using whole exome sequencing. Further minigene assay confirmed that the variation site affected splicing, causing protein truncation and affecting its function. Conclusion Clinical phenotype and minigene results suggest that WWOX gene homozygous variation c.172+1G>C can cause severe DEE. We also concluded that vigabatrin can effectively treat seizures. WWOX gene homozygous variation c.172+1G>C/p.? can cause asevere developmental epileptic encephalopathy, vigabatrin may be effective in treating seizures; according to minigene results, WWOX gene variation c.172+1G>C/p.? can cause WWOX protein truncation; WWOX gene variation can cause not only central nervous system injury but also peripheral nerve injury.