{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:19:44Z","timestamp":1785795584493,"version":"3.56.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,11,21]],"date-time":"2006-11-21T00:00:00Z","timestamp":1164067200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To report the clinical manifestations and functional aspects of Tuberous Sclerosis Complex (TSC), resulting from Codon 905 mutations in<jats:italic>TSC2<\/jats:italic>gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a detailed study of the TSC phenotype and genotype in a large French\u2010Canadian kindred (Family A). Subsequently, clinical and molecular data on 18 additional TSC families with missense mutations at the same codon of<jats:italic>TSC2<\/jats:italic>were collected. Functional studies were performed on the different missense changes and related to the phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 2714G&gt;A (R905Q) mutation was identified in Family A. The TSC phenotype in this family was unusually mild and characterized by hypomelanotic macules or focal seizures that remitted spontaneously or were easily controlled with medication. Diagnostic criteria were met in only a minority of mutation carriers. Other families with the R905Q mutation were found to have a similar mild phenotype. In contrast, patients with a 2713C&gt;T (R905W) or a 2713C&gt;G (R905G) mutation had more severe phenotypes. Although all three amino acid substitutions were pathogenic, the R905W and R905G substitutions affected tuberin function more severely than R905Q.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Codon 905 missense mutations in<jats:italic>TSC2<\/jats:italic>are relatively common. The<jats:italic>TSC2<\/jats:italic>R905Q mutation is associated with unusually mild disease, consistent with functional studies. Combined with previous reports, it is apparent that certain<jats:italic>TSC2<\/jats:italic>missense mutations are associated with a mild form of tuberous sclerosis, which in many patients does not meet standard diagnostic criteria. These findings have implications for the large number of patients with limited clinical features of TSC and for genetic counseling in these families.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21037","type":"journal-article","created":{"date-parts":[[2006,11,22]],"date-time":"2006-11-22T03:07:03Z","timestamp":1164164823000},"page":"528-539","source":"Crossref","is-referenced-by-count":97,"title":["Unusually mild tuberous sclerosis phenotype is associated with<i>TSC2<\/i>R905Q mutation"],"prefix":"10.1002","volume":"60","author":[{"given":"An C.","family":"Jansen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgur","family":"Sancak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Daniela","family":"D'Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanpreet","family":"Badhwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Gobbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Melanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Tampieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Koenekoop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke","family":"Maat\u2010Kievit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Goedbloed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans M. 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