{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T03:37:16Z","timestamp":1779161836673,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T00:00:00Z","timestamp":1487289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"TSC Rare Disease Clinical Research Network (RDCRN)","award":["1U54NS092090-01"],"award-info":[{"award-number":["1U54NS092090-01"]}]},{"name":"Autism Center of Excellence Network","award":["1U01NS082320-01"],"award-info":[{"award-number":["1U01NS082320-01"]}]},{"name":"RDCRN","award":["1U54NS092090-01"],"award-info":[{"award-number":["1U54NS092090-01"]}]},{"name":"BC Children's Hospital"},{"name":"Michelle Foundation"},{"name":"TS Association (UK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder with variable expressivity associated with hamartomatous tumors, abnormalities of the skin, and neurologic problems including seizures, intellectual disability, and autism. TSC is caused by pathogenic variants in either <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic>. In general, <jats:italic>TSC2<\/jats:italic> pathogenic variants are associated with a more severe phenotype than <jats:italic>TSC1<\/jats:italic> pathogenic variants. Here, we report a pathogenic <jats:italic>TSC2<\/jats:italic> variant, c.1864C&gt;T, p.(Arg622Trp), associated with a mild phenotype, with most carriers meeting fewer than two major clinical diagnostic criteria for TSC. This finding has significant implications for counseling patients regarding prognosis. More patient data are required before changing the surveillance recommendations for patients with the reported variant. However, consideration should be given to tailoring surveillance recommendations for all pathogenic <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> variants with documented milder clinical sequelae. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38083","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T13:51:08Z","timestamp":1487339468000},"page":"771-775","source":"Crossref","is-referenced-by-count":24,"title":["<i>TSC2<\/i> c.1864C&gt;T variant associated with mild cases of tuberous sclerosis complex"],"prefix":"10.1002","volume":"173","author":[{"given":"Laura S.","family":"Farach","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William T.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics BC Children's Hospital and UBC Vancouver, British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven P.","family":"Sparagana","sequence":"additional","affiliation":[{"name":"Division of Neurology Texas Scottish Rite Hospital for Children and University of Texas Southwestern Medical School Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Nellist","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connie T. 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M.","family":"Stumpel","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW) Maastricht University Medical Center (MUMC) Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marja","family":"Hietala","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Medical Biochemistry and Genetics University of Turku and Turku University Hospital Turku Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliott","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Imaging, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Division of Child and Adolescent Psychiatry, Department of Psychiatry, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan P.","family":"Creighton","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics BC Women's Hospital and UBC Vancouver, British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemiek","family":"Wagemans","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW) Maastricht University Medical Center (MUMC) Maastricht The Netherlands"},{"name":"Koraalgroep, Maasveld Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reveel","family":"Segel","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute Shaare Zedek Medical Center and the Hebrew University School of Medicine Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efrat","family":"Ben\u2010Shalom","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Shaare Zedek Medical Center Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kit Sing","family":"Au","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hope","family":"Northrup","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/316951"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22951"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370402"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21451"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21037"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.5.347"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12680"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.012757"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.08.001"},{"key":"e_1_2_5_12_1","unstructured":"NorthrupH KoenigMK PearsonDA AuKS. 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