Uncovering a Novel Variant in a Patient with Intellectual Disability Through BioinformaticsAnalysis

HERC۲-associated neurodevelopmental disorders (NDD) refer to a group of medical conditionsresulting from genetic mutations in the HERC۲ gene. These disorders can present a range of symptomsaffecting the brain and nervous system, such as delayed psychomotor development, severe mentalretardation, seizures, and autistic features. Whole exome sequencing (WES) was conducted on a tenyear-old male patient who was referred to the genetic center for genetic evaluation. To gain a deeperinsight into the effects of the mutation, a comprehensive analysis was carried out utilizingbioinformatics tools. The analysis of WES data revealed a homozygous single nucleotide alteration(C>T) at position c.۱۴۲۱۵ within exon ninety-two of the HERC۲ gene. This study demonstrated that thesubstitution of arginine with a stop codon in the Hect domain resulted in a premature stop codon atposition ۴۷۳۹. This mutation substantially disrupts the exonic splicing enhancer (ESE) element in exonninety-two, potentially leading to exon skipping.The discovery of a novel pathogenic variant situatedwithin exon ninety-two of the HERC۲ gene is significant due to its association with an autosomalrecessive inheritance pattern in cases of intellectual developmental disorder (IDD). Ultimately, thisvariant may contribute to the underlying mechanisms that lead to the onset of intellectual developmentaldisorder.

کلیدواژه ها:

HERC۲ gene ، novel variant ، synapse development