Implications of a De Novo Variant in the SOX12 Gene in a Patient with Generalized Epilepsy, Intellectual Disability, and Childhood Emotional Behavioral Disorders

• Published in: Current Issues in Molecular Biology Vol. 46; no. 7; pp. 6407 - 6422
• Main Authors: Treccarichi, Simone, Calì, Francesco, Vinci, Mirella, Ragalmuto, Alda, Musumeci, Antonino, Federico, Concetta, Costanza, Carola, Bottitta, Maria, Greco, Donatella, Saccone, Salvatore, Elia, Maurizio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2024
• Subjects: Amino acids; Behavior; Child psychopathology; Children; Disability; DNA sequencing; Epilepsy; Genes; Genetic transcription; Levetiracetam; neurodevelopmental delay; Neurophysiology; next generation sequencing; Nucleotide sequencing; SOX12 gene; epilepsy; neurodevelopmental delay; SOX12 gene; next generation sequencing
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb46070383

( ) genes, a recently discovered gene family, play crucial roles in the regulation of neuronal stem cell proliferation and glial differentiation during nervous system development and neurogenesis. Whole exome sequencing (WES) in patients presenting with generalized epilepsy, intellectual disability, and childhood emotional behavioral disorder, uncovered a variation within gene. Notably, this gene has never been associated with neurodevelopmental disorders. No variants in known genes linked with the patient's symptoms have been detected by the WES Trio analysis. To date, any MIM phenotype number associated with intellectual developmental disorder has not been assigned for . In contrast, both and genes within the same C group ( ) of the gene family have been associated with neurodevelopmental disorders. The variant identified in the patient here described was situated within the critical high-mobility group (HMG) functional site of the protein. This domain, in the Sox protein family, is essential for DNA binding and bending, as well as being responsible for transcriptional activation or repression during the early stages of gene expression. Sequence alignment within ( , and ) revealed a high conservation rate of the HMG region. The in silico predictive analysis described this novel variant as likely pathogenic. Furthermore, the mutated protein structure predictions unveiled notable changes with potential deleterious effects on the protein structure. The aim of this study is to establish a correlation between the gene and the symptoms diagnosed in the patient.