Show simple item record

dc.contributor.authorWeerts, M. J. A.
dc.contributor.authorLanko, K.
dc.contributor.authorGuzmán-Vega, F. J.
dc.contributor.authorJackson, A.
dc.contributor.authorRamakrishnan, R.
dc.contributor.authorCardona-Londoño, K. J.
dc.contributor.authorPeña-Guerra, K. A.
dc.contributor.authorvan Bever, Y.
dc.contributor.authorvan Paassen, B. W.
dc.contributor.authorKievit, A.
dc.contributor.authorvan Slegtenhorst, M.
dc.contributor.authorAllen, N. M.
dc.contributor.authorKehoe, C. M.
dc.contributor.authorRobinson, H. K.
dc.contributor.authorPang, L.
dc.contributor.authorBanu, S. H.
dc.contributor.authorZaman, M.
dc.contributor.authorEfthymiou, S.
dc.contributor.authorHoulden, H.
dc.contributor.authorJärvelä, I.
dc.contributor.authorLauronen, L.
dc.contributor.authorMäättä, T.
dc.contributor.authorSchrauwen, I.
dc.contributor.authorLeal, S. M.
dc.contributor.authorRuivenkamp, C. A. L.
dc.contributor.authorBarge-Schaapveld, Dqcm
dc.contributor.authorPeeters-Scholte, Cmpcd
dc.contributor.authorGalehdari, H.
dc.contributor.authorMazaheri, N.
dc.contributor.authorSisodiya, S. M.
dc.contributor.authorHarrison, V.
dc.contributor.authorSun, A.
dc.contributor.authorThies, J.
dc.contributor.authorPedroza, L. A.
dc.contributor.authorLara-Taranchenko, Y.
dc.contributor.authorChinn, I. K.
dc.contributor.authorLupski, J. R.
dc.contributor.authorGarza-Flores, A.
dc.contributor.authorMcGlothlin, J.
dc.contributor.authorYang, L.
dc.contributor.authorHuang, S.
dc.contributor.authorWang, X.
dc.contributor.authorJewett, T.
dc.contributor.authorRosso, G.
dc.contributor.authorLin, X.
dc.contributor.authorMohammed, S.
dc.contributor.authorMerritt, J. L., 2nd
dc.contributor.authorMirzaa, G. M.
dc.contributor.authorTimms, A. E.
dc.contributor.authorScheck, J.
dc.contributor.authorElting, M. W.
dc.contributor.authorPolstra, A. M.
dc.contributor.authorSchenck, L.
dc.contributor.authorRuzhnikov, M. R. Z.
dc.contributor.authorVetro, A.
dc.contributor.authorMontomoli, M.
dc.contributor.authorGuerrini, R.
dc.contributor.authorKoboldt, D. C.
dc.contributor.authorMosher, T. M.
dc.contributor.authorPastore, M. T.
dc.contributor.authorMcBride, K. L.
dc.contributor.authorPeng, J.
dc.contributor.authorPan, Z.
dc.contributor.authorWillemsen, M.
dc.contributor.authorKoning, S.
dc.contributor.authorTurnpenny, P. D.
dc.contributor.authorde Vries, B. B. A.
dc.contributor.authorGilissen, C.
dc.contributor.authorPfundt, R.
dc.contributor.authorLees, M.
dc.contributor.authorBraddock, S. R.
dc.contributor.authorKlemp, K. C.
dc.contributor.authorVansenne, F.
dc.contributor.authorvan Gijn, M. E.
dc.contributor.authorQuindipan, C.
dc.contributor.authorDeardorff, M. A.
dc.contributor.authorHamm, J. A.
dc.contributor.authorPutnam, A. M.
dc.contributor.authorBaud, R.
dc.contributor.authorWalsh, L.
dc.contributor.authorLynch, S. A.
dc.contributor.authorBaptista, J.
dc.contributor.authorPerson, R. E.
dc.contributor.authorMonaghan, K. G.
dc.contributor.authorCrunk, A.
dc.contributor.authorKeller-Ramey, J.
dc.contributor.authorReich, A.
dc.contributor.authorElloumi, H. Z.
dc.contributor.authorAlders, M.
dc.contributor.authorKerkhof, J.
dc.contributor.authorMcConkey, H.
dc.contributor.authorHaghshenas, S.
dc.contributor.authorMaroofian, R.
dc.contributor.authorSadikovic, B.
dc.contributor.authorBanka, S.
dc.contributor.authorArold, S. T.
dc.contributor.authorBarakat, T. S.
dc.identifier.citationGenet Med. 2021 Aug 3. doi: 10.1038/s41436-021-01246-2.
dc.description.abstractPURPOSE: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. METHODS: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. RESULTS: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. CONCLUSION: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.
dc.rights© 2021. The Author(s).
dc.titleDelineating the molecular and phenotypic spectrum of the SETD1B-related syndrome
dc.typeJournal Article
dc.identifier.journalGenetics in medicine
dc.description.noteRD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.
dc.description.admin-noteAccepted version (6 month embargo), submitted version

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record