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dc.contributor.authorSearle, Claire
dc.contributor.authorVasudevan, Pradeep
dc.date.accessioned2022-01-28T14:19:29Z
dc.date.available2022-01-28T14:19:29Z
dc.date.issued2021
dc.identifier.citationPoole, R. L., Curry, P., Marcinkute, R., Brewer, C., Coman, D., Hobson, E., Johnson, D., Lynch, S. A., Saggar, A., Searle, C., Scurr, I., Turnpenny, P. D., Vasudevan, P., & Tatton-Brown, K. (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, 185(8), 2445–2454. https://doi.org/10.1002/ajmg.a.62350en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12904/15125
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.description.urihttps://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.62350en_US
dc.language.isoenen_US
dc.subjectMTORen_US
dc.subjectSmith-Kingsmore syndromeen_US
dc.subjectmegalencephalyen_US
dc.titleDelineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense varianten_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecordhttps://doi.org/10.1002/ajmg.a.62350en_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.panelUnspecifieden_US
refterms.dateFirstOnline2021
html.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.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


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