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There have been several recent advances that elucidate the genetic complex of this disorder that will help understand the basic neurobiology of this disorder. We report a Tunisian patient with clinical manifestations of TSC syndrome. We investigated the causative molecular defect in this patient using PCR followed by direct sequencing. Subsequently, in silico studies and mRNA analysis were performed to study the pathogenicity of the new variation found in the <jats:italic>TSC2<\/jats:italic>. Bioinformatics tools predicted that the novel mutation c.1444\u20102A&gt;T have pathogenic effects on splicing machinery. RT\u2010PCR followed by sequencing revealed that the mutation c.1444\u20102A&gt;T generates two aberrant transcripts. The first, with exon 15 skipping, is responsible for the loss of 52 amino acids, which causes the production of an aberrant protein isoform. The second, with the inclusion of 122 nucleotides of intron 14, is responsible for the creation of new premature termination codons (TGA), which causes the production of a truncated TSC2 protein. This study highlighted the clinical features of a Tunisian patient with TSC syndrome and revealed a splicing mutation c.1444\u20102A&gt;T within intron 14 of <jats:italic>TSC2<\/jats:italic> gene, which is present for the first time using Sanger sequencing approach, as a disease\u2010causing mutation in a Tunisian patient with TSC syndrome.<\/jats:p>","DOI":"10.1002\/iub.2134","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T08:30:44Z","timestamp":1563438644000},"page":"1937-1945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel de novo splicing mutation c.1444\u20102A&gt;T in the <i>TSC2<\/i> gene causes exon skipping and premature termination in a patient with tuberous sclerosis 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