# Splicing Analysis of Exonic TSC1 and TSC2 Gene Variants Causing Tuberous Sclerosis Complex

## TL;DR

This study explores how mutations in TSC1 and TSC2 genes affect splicing, leading to conditions like Tuberous Sclerosis Complex.

## Contribution

The study identifies 10 splicing-affected mutations in TSC1 and TSC2 using bioinformatics and minigene analysis.

## Key findings

- Mutations in TSC1 and TSC2 disrupt splicing, causing exon skipping or intron retention.
- Bioinformatics and minigene analysis confirmed 10 candidate mutations impacting pre-mRNA splicing.
- The findings highlight the importance of splicing analysis in evaluating pathogenic TSC variants.

## Abstract

Tuberous sclerosis complex (TSC) is characterized by abnormalities in cell proliferation and migration, leading to the development of hamartomas, benign tumors, or malignant cancers, affecting both the skin and brain, as well as potentially impacting the heart, kidneys, lungs, and eyes, with varying patterns of involvement over a lifetime. It is primarily caused by mutations in the TSC1 and TSC2 genes. Aberrant splicing is a crucial factor in hereditary diseases. Alternative splicing is a key mechanism for expanding the diversity of the human proteome. Mutations disrupting canonical splice sites or splicing regulatory elements impede the utilization of splice sites, leading to exon skipping and intron retention. We comprehensively analyzed missense and nonsense mutations of TSC1 and TSC2 genes using bioinformatics tools and identified 10 candidate mutations affecting pre-mRNA splicing through minigene analysis. Mutations in TSC genes can lead to partial or complete exon skipping and/or intron retention through complex mechanisms. This study emphasizes the importance of evaluating their roles in the splicing of suspected pathogenic variants in TSC.