23 DOI: https://doi.org/10.1016/j.jgeb.2026.100758 English eng Chuanjie Zhang Contributor <div class="abstract author" id="as0005" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0010" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Objective</h3><div class="u-margin-s-bottom" id="sp0045" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">To explore the molecular mechanism of tuberous sclerosis type 2 caused by <em style="margin: 0px; padding: 0px;">TSC2</em> synonymous mutations affecting normal splicing of precursor mRNA.</div></div><div class="abstract author" id="as0010" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0015" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Methods</h3><div class="u-margin-s-bottom" id="sp0050" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">Review and analyses clinical diagnosis and treatment process of a patient with tuberous sclerosis complex type 2, summarize the relationship between genotype and clinical phenotype. Use bioinformatics methods to analyses the effect of <em style="margin: 0px; padding: 0px;">TSC2</em> gene synonymous mutations on precursor mRNA splicing and use in vivo splicing experiments and in vitro minigene experiments to verify the possible pathogenic mechanism of <em style="margin: 0px; padding: 0px;">TSC2</em> gene synonymous mutations.</div></div><div class="abstract author" id="as0015" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0020" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Results</h3><div class="u-margin-s-bottom" id="sp0055" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">The proband exhibited tuberous sclerosis phenotype including epilepsy and depigmentation. A synonymous mutation in the <em style="margin: 0px; padding: 0px;">TSC2</em> gene (c.1443G > A, p.Glu481=) associated with the phenotype was identified. Bioinformatics analysis suggested that this synonymous mutation may disrupt normal pre-mRNA splicing. Both in vivo splicing assays and minigene experiments confirmed that the synonymous mutation indeed affects proper pre-mRNA splicing.</div></div><div class="abstract author" id="as0020" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0025" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Conclusion</h3><div class="u-margin-s-bottom" id="sp0060" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><em style="margin: 0px; padding: 0px;">TSC2</em> c.1443G > A (p.Glu481=) synonymous mutation may be associated with tuberous sclerosis type 2 by disrupting normal pre-mRNA splicing.</div></div> Elsevier September 2026 pdf Journal of Genetic Engineering and Biotechnology A novel synonymous TSC2 mutation in a Chinese family leads to tuberous sclerosis type 2 by disrupting Normal pre-mRNA splicing mixed material Elsevier