{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:08:01Z","timestamp":1790716081121,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GINOP","award":["2.3.2-15-2016-00039"],"award-info":[{"award-number":["2.3.2-15-2016-00039"]}]},{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["PD115677"],"award-info":[{"award-number":["PD115677"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Approximately fifteen percent of patients with tuberous sclerosis complex (TSC) phenotype do not have any genetic disease-causing mutations which could be responsible for the development of TSC. The lack of a proper diagnosis significantly affects the quality of life for these patients and their families. Methods: The aim of our study was to use Whole Exome Sequencing (WES) in order to identify the genes responsible for the phenotype of nine patients with clinical signs of TSC, but without confirmed tuberous sclerosis complex 1\/ tuberous sclerosis complex 2 (TSC1\/TSC2) mutations using routine molecular genetic diagnostic tools. Results: We found previously overlooked heterozygous nonsense mutations in TSC1, and a heterozygous intronic variant in TSC2. In one patient, two heterozygous missense variants were found in polycystic kidney and hepatic disease 1 (PKHD1), confirming polycystic kidney disease type 4. A heterozygous missense mutation in solute carrier family 12 member 5 (SLC12A5) was found in one patient, which is linked to cause susceptibility to idiopathic generalized epilepsy type 14. Heterozygous nonsense variant ring finger protein 213 (RNF213) was identified in one patient, which is associated with susceptibility to Moyamoya disease type 2. In the remaining three patients WES could not reveal any variants clinically relevant to the described phenotypes. Conclusion: Patients without appropriate diagnosis due to the lack of sensitivity of the currently used routine diagnostic methods can significantly profit from the wider application of next generation sequencing technologies in order to identify genes and variants responsible for their symptoms.<\/jats:p>","DOI":"10.3390\/genes12091401","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"1401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Whole Exome Sequencing in a Series of Patients with a Clinical Diagnosis of Tuberous Sclerosis Not Confirmed by Targeted TSC1\/TSC2 Sequencing"],"prefix":"10.3390","volume":"12","author":[{"given":"Erzsebet","family":"Kovesdi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"},{"name":"Molecular Neuroendocrinology Research Group, Institute of Physiology, Center for Neuroscience, Szentagothai Research Center, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reka","family":"Ripszam","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etelka","family":"Postyeni","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emese Beatrix","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kelemen","sequence":"additional","affiliation":[{"name":"National Institute of Clinical Neurosciences, 1145 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Fabos","sequence":"additional","affiliation":[{"name":"Somogy County Mor Kaposi Teaching Hospital, 7400 Kaposvar, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Farkas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Semmelweis University, 1085-Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Hadzsiev","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Sumegi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"},{"name":"Departments of Biochemistry and Medical Chemistry, Medical School, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Magyari","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar Guatibonza","family":"Moreno","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Melegh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical School, Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1749-6632.1991.tb37754.x","article-title":"Epidemiology of tuberous sclerosis","volume":"615","author":"Osborne","year":"1991","journal-title":"Ann. 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