{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:12:16Z","timestamp":1780420336188,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Tuberous sclerosis complex (TSC) is a variable multisystem disorder. The \u201cno mutations identified\u201d (NMI) group are reportedly phenotypically milder than those with an identified molecular cause, and often have mosaic or intronic variants not detected by standard sequencing methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe the phenotypes in an Australian TSC NMI group (<jats:italic>n<\/jats:italic>\u2009=\u200918) and a molecular testing strategy implementable in a diagnostic laboratory. Massively parallel sequencing (MPS) of the whole genomic regions of <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> was performed using DNA extracted from multiple tissue samples per participant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study showed that the phenotype in TSC NMI individuals can be similar to those with heterozygous, particularly <jats:italic>TSC1<\/jats:italic>, variants. Although neurodevelopmental outcomes can be less severe, the number of organ systems involved was similar to the non\u2010mosaic groups. A diagnostic yield of 72% (13\/18) was achieved, with the majority (10\/13) being mosaic variants and the remainder heterozygous variants missed on previous testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Testing DNA from multiple tissue samples allowed for validation of otherwise discarded low\u2010level mosaic variants and detection of mosaic variants by MPS without excessive cost or the need for specialised techniques. Implementing this approach in a diagnostic setting is viable and allows optimal clinical care of patients with NMI TSC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70017","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T13:32:57Z","timestamp":1727789577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deep Sequencing and Phenotyping in an Australian Tuberous Sclerosis Complex \u201cNo Mutations Identified\u201d Cohort"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1319-7570","authenticated-orcid":false,"given":"Clara\u00a0W.\u00a0T.","family":"Chung","sequence":"first","affiliation":[{"name":"Centre for Clinical Genetics, Sydney Children's Hospital  Randwick New South Wales Australia"},{"name":"Tuberous Sclerosis Management Clinic, Sydney Children's Hospital  Randwick New South Wales Australia"},{"name":"Discipline of Paediatrics and 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Health UNSW Sydney  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra\u00a0T.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Kids Neuroscience Centre, Kids Research Children's Hospital at Westmead  Westmead New South Wales Australia"},{"name":"The Children's Medical Research Institute  Westmead New South Wales Australia"},{"name":"Specialty of Child and Adolescent Health, Sydney Medical School University of Sydney  Camperdown New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin\u00a0P.","family":"Kirk","sequence":"additional","affiliation":[{"name":"Centre for Clinical Genetics, Sydney Children's Hospital  Randwick New South Wales Australia"},{"name":"Discipline of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Medicine and Health UNSW Sydney  New South Wales Australia"},{"name":"NSW Health Pathology Randwick Genomics Laboratory Prince of Wales Hospital 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