000075581 001__ 75581 000075581 005__ 20190709135427.0 000075581 0247_ $$2doi$$a10.1002/ajmg.a.38279 000075581 0248_ $$2sideral$$a99854 000075581 037__ $$aART-2017-99854 000075581 041__ $$aeng 000075581 100__ $$aHuisman, S. 000075581 245__ $$aPhenotypes and genotypes in individuals with SMC1A variants 000075581 260__ $$c2017 000075581 5060_ $$aAccess copy available to the general public$$fUnrestricted 000075581 5203_ $$aSMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes. 000075581 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B20$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00707 000075581 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000075581 590__ $$a2.264$$b2017 000075581 591__ $$aGENETICS & HEREDITY$$b100 / 171 = 0.585$$c2017$$dQ3$$eT2 000075581 592__ $$a1.098$$b2017 000075581 593__ $$aGenetics (clinical)$$c2017$$dQ2 000075581 593__ $$aGenetics$$c2017$$dQ2 000075581 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000075581 700__ $$aMulder, P.A. 000075581 700__ $$aRedeker, E. 000075581 700__ $$aBader, I. 000075581 700__ $$aBisgaard, A.-M. 000075581 700__ $$aBrooks, A. 000075581 700__ $$aCereda, A. 000075581 700__ $$aCinca, C. 000075581 700__ $$aClark, D. 000075581 700__ $$aCormier-Daire, V. 000075581 700__ $$aDeardorff, M.A. 000075581 700__ $$aDiderich, K. 000075581 700__ $$aElting, M. 000075581 700__ $$avan Essen, A. 000075581 700__ $$aFitzPatrick , D. 000075581 700__ $$aGervasini, C. 000075581 700__ $$aGillessen-Kaesbach, G. 000075581 700__ $$aGirisha, K.M. 000075581 700__ $$aHilhorst-Hofstee, Y. 000075581 700__ $$aHopman, S. 000075581 700__ $$aHorn, D. 000075581 700__ $$aIsrie, M. 000075581 700__ $$aJansen, S. 000075581 700__ $$aJespersgaard, C. 000075581 700__ $$aKaiser, F.J. 000075581 700__ $$aKaur, M. 000075581 700__ $$aKleefstra, T. 000075581 700__ $$aKrantz, I.D. 000075581 700__ $$aLakeman, P. 000075581 700__ $$aLandlust, A. 000075581 700__ $$aLessel, D. 000075581 700__ $$aMichot, C. 000075581 700__ $$aMoss, J. 000075581 700__ $$aNoon, S.E. 000075581 700__ $$aOliver, C. 000075581 700__ $$aParenti, I. 000075581 700__ $$0(orcid)0000-0003-3203-6254$$aPie, J.$$uUniversidad de Zaragoza 000075581 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, F.J.$$uUniversidad de Zaragoza 000075581 700__ $$aRieubland, C. 000075581 700__ $$aRusso, S. 000075581 700__ $$aSelicorni, A. 000075581 700__ $$aTümer, Z. 000075581 700__ $$aVorstenbosch, R. 000075581 700__ $$aWenger, T.L. 000075581 700__ $$avan Balkom, I. 000075581 700__ $$aPiening, S. 000075581 700__ $$aWierzba, J. 000075581 700__ $$aHennekam, R.C. 000075581 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología 000075581 7102_ $$11010$$2670$$aUniversidad de Zaragoza$$bDpto. Pediatría Radiol.Med.Fís$$cÁrea Pediatría 000075581 773__ $$g173, 8 (2017), 2108-2125$$pAm. J. Med. Genet. A$$tAMERICAN JOURNAL OF MEDICAL GENETICS PART A$$x1552-4825 000075581 8564_ $$s414581$$uhttps://zaguan.unizar.es/record/75581/files/texto_completo.pdf$$yPostprint 000075581 8564_ $$s95685$$uhttps://zaguan.unizar.es/record/75581/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000075581 909CO $$ooai:zaguan.unizar.es:75581$$particulos$$pdriver 000075581 951__ $$a2019-07-09-11:29:52 000075581 980__ $$aARTICLE