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Four different molecular techniques were implemented to identify from single nucleotide variants to large rearrangements in the <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> genes of 66 unrelated Mexican-descent patients that clinically fulfilled the criteria for a definitive TSC diagnosis. The mutation detection rate was 94%, <jats:italic>TSC2<\/jats:italic> pathogenic variants (PV) prevailed over <jats:italic>TSC1<\/jats:italic> PV (77% vs. 23%) and a recurrent mutation site (hotspot) was observed in <jats:italic>TSC1<\/jats:italic> exon 15. Interestingly, 40% of the identified mutations had not been previously reported. The wide range of novels PV made it difficult to establish any genotype-phenotype correlation, but most of the PV conditioned neurological involvement (intellectual disability and epilepsy). Our 3D protein modeling of two variants classified as likely pathogenic demonstrated that they could alter the structure and function of the hamartin (<jats:italic>TSC1<\/jats:italic>) or tuberin (<jats:italic>TSC2<\/jats:italic>) proteins. Molecular analyses of parents and first-degree affected family members of the index cases enabled us to distinguish familial (18%) from sporadic (82%) cases and to identify one case of apparent gonadal mosaicism.<\/jats:p>","DOI":"10.1038\/s41598-020-62759-5","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T10:03:07Z","timestamp":1587376987000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["First comprehensive TSC1\/TSC2 mutational analysis in Mexican patients with Tuberous Sclerosis Complex reveals numerous novel pathogenic variants"],"prefix":"10.1038","volume":"10","author":[{"given":"Miriam E.","family":"Reyna-Fabi\u00e1n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Hern\u00e1ndez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Alc\u00e1ntara-Ortigoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge T.","family":"Ayala-Sumuano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Enr\u00edquez-Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Vel\u00e1zquez-Arag\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Varela-Echavarr\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos G.","family":"Todd-Qui\u00f1ones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"Gonz\u00e1lez-del Angel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,20]]},"reference":[{"key":"62759_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-018-0870-y","volume":"13","author":"D Ebrahimi-Fakhari","year":"2018","unstructured":"Ebrahimi-Fakhari, D. et al. 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