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dc.contributor.authorPoole, Rebecca L.
dc.contributor.authorCurry, Philippa D. K.
dc.contributor.authorMarcinkute, Ruta
dc.contributor.authorBrewer, Carole
dc.contributor.authorComan, David
dc.contributor.authorHobson, Emma
dc.contributor.authorJohnson, Diana
dc.contributor.authorLynch, Sally Ann
dc.contributor.authorSaggar, Anand
dc.contributor.authorSearle, Claire
dc.contributor.authorScurr, Ingrid
dc.contributor.authorTurnpenny, Peter D.
dc.contributor.authorVasudevan, Pradeep
dc.contributor.authorTatton-Brown, Katrina
dc.date.accessioned2021-10-01T13:38:51Z
dc.date.available2021-10-01T13:38:51Z
dc.date.issued2021-05-25
dc.identifier.citationPoole, R. L. et al. (2021) ‘Delineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense variant.’, American journal of medical genetics. Part A. doi: 10.1002/ajmg.a.62350.
dc.identifier.pmid34032352
dc.identifier.doi10.1002/ajmg.a.62350
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/622120
dc.description.abstractSmith-Kingsmore Syndrome (SKS) is a rare genetic syndrome associated with megalencephaly, a variable intellectual disability, autism spectrum disorder, and MTOR gain of function variants. Only 30 patients with MTOR missense variants are published, including 14 (47%) with the MTOR c.5395G>A p.(Glu1799Lys) variant. Limited phenotypic data impacts the quality of information delivered to families and the robustness of interpretation of novel MTOR missense variation. This study aims to improve our understanding of the SKS phenotype through the investigation of 16 further patients with the MTOR c.5395G>A p.(Glu1799Lys) variant. Through the careful phenotypic evaluation of these 16 patients and integration with data from 14 previously reported patients, we have defined major (100% patients) and frequent (>15%) SKS clinical characteristics and, using these data, proposed guidance for evidence-based management. In addition, in the absence of functional studies, we suggest that the combination of the SKS major clinical features of megalencephaly (where the head circumference is at least 3SD) and an intellectual disability with a de novo MTOR missense variant (absent from population databases) should be considered diagnostic for SKS.
dc.language.isoeng
dc.publisherWiley
dc.relation.urlhttps://doi.org/10.1002/ajmg.a.62350
dc.rights© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/
dc.subjectmegalencephaly
dc.subjectMTOR
dc.subjectSmith-Kingsmore syndrome
dc.titleDelineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense variant
dc.typeJournal Article
dc.identifier.journalAmerican journal of medical genetics. Part A
dc.description.noteThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.
dc.type.versionPublished
dc.description.admin-notePublished version, accepted version (12 month embargo)


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© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
Except where otherwise noted, this item's license is described as © 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.