MED23 pathogenic variant: genomic-phenotypic analysis

• Published in: Journal of medicine and life 2024-05, Vol.17 (5), p.500-507
• Main Authors: Bamaga, Ahmed, Muthaffar, Osama, Alyazidi, Anas, Bahowarth, Sarah, Shawli, Mohammed, Alotibi, Fahad, Alsehemi, Matar, Almohammal, Mohammad, Alawwadh, Adel, Alghamdi, Njood
• Format: Article
• Language: English
• Subjects: Bioinformatics; Case reports; Child; Child development; Convulsions & seizures; DNA Copy Number Variations - genetics; Electroencephalography; Epilepsy; Exome Sequencing; Family medical history; Female; Genes; Genetic testing; Genomes; Genomic analysis; Genomics - methods; Genotype & phenotype; Humans; Intellectual disabilities; Intellectual Disability - genetics; Magnetic resonance imaging; Male; Mediator Complex - genetics; Medical imaging; Mutation; Mutation - genetics; Myogenesis; Neuroimaging; Original; Parents & parenting; Patients; Phenotype
• ISSN: 1844-122X; 1844-3117; 1844-3117
• DOI: 10.25122/jml-2024-0065

The mediator complex subunit 23 ( ) gene encodes a protein that acts as a tail module mediator complex, a multi-subunit co-activator involved in several cellular activities. has been shown to have substantial roles in myogenesis and other molecular mechanisms. The functions of in the neurological system remain unclear and the clinical phenotype is not thoroughly described. Whole exome sequencing was used to identify a novel mutation in the gene. DNA capture probes using next-generation sequencing-based copy number variation analysis with Illumina array were performed. The clinical, demographic, neuroimaging, and electrophysiological data of the patients were collected, and similarly, the data of all reported cases in the literature were extracted to compare findings. Screening a total of 9,662 articles, we identified 22 main regulatory processes for the gene, including suppressive activity for carcinogenic processes. is also involved in the brain's neurogenesis and functions. The identified cases mainly presented with intellectual disability (87.5%) and developmental delay (50%). Seizures were present in only 18.75% of the patients. Slow backgrounds and spike and sharp-wave complexes were reported on the electroencephalogram (EEG) of a few patients and delayed myelination, thin corpus callosum, and pontine hypoplasia on magnetic resonance imaging (MRI). The gene regulates several processes in which its understanding promotes considerable therapeutic potential for patients. It is crucial to consider genetic and laboratory testing, particularly when encountering potential carriers. Intellectual disability and developmental delay are the most notable clinical signs with heterogeneous features on EEG and MRI.