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dc.contributor.authorRadio, Francesca Clementina
dc.contributor.authorPang, Kaifang
dc.contributor.authorCiolfi, Andrea
dc.contributor.authorLevy, Michael A.
dc.contributor.authorHernández-García, Andrés
dc.contributor.authorPedace, Lucia
dc.contributor.authorPantaleoni, Francesca
dc.contributor.authorLiu, Zhandong
dc.contributor.authorde Boer, Elke
dc.contributor.authorJackson, Adam
dc.contributor.authorBruselles, Alessandro
dc.contributor.authorMcConkey, Haley
dc.contributor.authorStellacci, Emilia
dc.contributor.authorLo Cicero, Stefania
dc.contributor.authorMotta, Marialetizia
dc.contributor.authorCarrozzo, Rosalba
dc.contributor.authorDentici, Maria Lisa
dc.contributor.authorMcWalter, Kirsty
dc.contributor.authorDesai, Megha
dc.contributor.authorMonaghan, Kristin G.
dc.contributor.authorTelegrafi, Aida
dc.contributor.authorPhilippe, Christophe
dc.contributor.authorVitobello, Antonio
dc.contributor.authorAu, Margaret
dc.contributor.authorGrand, Katheryn
dc.contributor.authorSanchez-Lara, Pedro A.
dc.contributor.authorBaez, Joanne
dc.contributor.authorLindstrom, Kristin
dc.contributor.authorKulch, Peggy
dc.contributor.authorSebastian, Jessica
dc.contributor.authorMadan-Khetarpal, Suneeta
dc.contributor.authorRoadhouse, Chelsea
dc.contributor.authorMacKenzie, Jennifer J.
dc.contributor.authorMonteleone, Berrin
dc.contributor.authorSaunders, Carol J.
dc.contributor.authorJean Cuevas, July K.
dc.contributor.authorCross, Laura
dc.contributor.authorZhou, Dihong
dc.contributor.authorHartley, Taila
dc.contributor.authorSawyer, Sarah L.
dc.contributor.authorMonteiro, Fabíola Paoli
dc.contributor.authorSecches, Tania Vertemati
dc.contributor.authorKok, Fernando
dc.contributor.authorSchultz-Rogers, Laura E.
dc.contributor.authorMacke, Erica L.
dc.contributor.authorMorava, Eva
dc.contributor.authorKlee, Eric W.
dc.contributor.authorKemppainen, Jennifer
dc.contributor.authorIascone, Maria
dc.contributor.authorSelicorni, Angelo
dc.contributor.authorTenconi, Romano
dc.contributor.authorAmor, David J.
dc.contributor.authorPais, Lynn
dc.contributor.authorGallacher, Lyndon
dc.contributor.authorTurnpenny, Peter D.
dc.contributor.authorStals, Karen
dc.contributor.authorEllard, Sian
dc.contributor.authorCabet, Sara
dc.contributor.authorLesca, Gaetan
dc.contributor.authorPascal, Joset
dc.contributor.authorSteindl, Katharina
dc.contributor.authorRavid, Sarit
dc.contributor.authorWeiss, Karin
dc.contributor.authorCastle, Alison M. R.
dc.contributor.authorCarter, Melissa T.
dc.contributor.authorKalsner, Louisa
dc.contributor.authorde Vries, Bert B. A.
dc.contributor.authorvan Bon, Bregje W.
dc.contributor.authorWevers, Marijke R.
dc.contributor.authorPfundt, Rolph
dc.contributor.authorStegmann, Alexander P. A.
dc.contributor.authorKerr, Bronwyn
dc.contributor.authorKingston, Helen M.
dc.contributor.authorChandler, Kate E.
dc.contributor.authorSheehan, Willow
dc.contributor.authorElias, Abdallah F.
dc.contributor.authorShinde, Deepali N.
dc.contributor.authorTowne, Meghan C.
dc.contributor.authorRobin, Nathaniel H.
dc.contributor.authorGoodloe, Dana
dc.contributor.authorVanderver, Adeline
dc.contributor.authorSherbini, Omar
dc.contributor.authorBluske, Krista
dc.contributor.authorHagelstrom, R. Tanner
dc.contributor.authorZanus, Caterina
dc.contributor.authorFaletra, Flavio
dc.contributor.authorMusante, Luciana
dc.contributor.authorKurtz-Nelson, Evangeline C.
dc.contributor.authorEarl, Rachel K.
dc.contributor.authorAnderlid, Britt-Marie
dc.contributor.authorMorin, Gilles
dc.contributor.authorvan Slegtenhorst, Marjon
dc.contributor.authorDiderich, Karin E. M.
dc.contributor.authorBrooks, Alice S.
dc.contributor.authorGribnau, Joost
dc.contributor.authorBoers, Ruben G.
dc.contributor.authorFinestra, Teresa Robert
dc.contributor.authorCarter, Lauren B.
dc.contributor.authorRauch, Anita
dc.contributor.authorGasparini, Paolo
dc.contributor.authorBoycott, Kym M.
dc.contributor.authorBarakat, Tahsin Stefan
dc.contributor.authorGraham, John M. Jr
dc.contributor.authorFaivre, Laurence
dc.contributor.authorBanka, Siddharth
dc.contributor.authorWang, Tianyun
dc.contributor.authorEichler, Evan E.
dc.contributor.authorPriolo, Manuela
dc.contributor.authorDallapiccola, Bruno
dc.contributor.authorVissers, Lisenka E. L. M.
dc.contributor.authorSadikovic, Bekim
dc.contributor.authorScott, Daryl A.
dc.contributor.authorHolder, Jimmy Lloyd Jr
dc.contributor.authorTartaglia, Marco
dc.date.accessioned2021-10-01T12:24:00Z
dc.date.available2021-10-01T12:24:00Z
dc.date.issued2021-03-04
dc.identifier.citationRadio, F. C. et al. (2021) ‘SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.’, American journal of human genetics, 108(3), pp. 502–516. doi: 10.1016/j.ajhg.2021.01.015.
dc.identifier.pmid33596411
dc.identifier.doi10.1016/j.ajhg.2021.01.015
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/622098
dc.description.abstractDeletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.
dc.language.isoeng
dc.publisherCell Press
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0002-9297(21)00015-X
dc.rightsCopyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/
dc.subjectChild
dc.subjectHumans
dc.subjectAdolescent
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subject*obesity
dc.subject*neurodevelopmental disorder
dc.subjectChild, Preschool
dc.subjectChromosome Deletion
dc.subjectPhenotype
dc.subject*1p36
dc.subject*distal 1p36 deletion syndrome
dc.subject*DNA methylome analysis
dc.subject*episignature
dc.subject*genotype-phenotype correlations
dc.subject*proximal 1p36 deletion syndrome
dc.subject*SPEN
dc.subject*X chromosome
dc.subjectAutism Spectrum Disorder/genetics/pathology
dc.subjectChromosome Disorders/*genetics/physiopathology
dc.subjectChromosomes, Human, Pair 1/*genetics
dc.subjectChromosomes, Human, X/*genetics
dc.subjectDNA Methylation/genetics
dc.subjectDNA-Binding Proteins/*genetics
dc.subjectEpigenesis, Genetic/genetics
dc.subjectHaploinsufficiency/genetics
dc.subjectIntellectual Disability/genetics/physiopathology
dc.subjectNeurodevelopmental Disorders/genetics/physiopathology
dc.subjectRNA-Binding Proteins/*genetics
dc.titleSPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females
dc.typeJournal Article
dc.identifier.journalAmerican journal of human genetics
dc.identifier.pmcidPMC8008487
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 (6 month embargo), submitted version


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Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Except where otherwise noted, this item's license is described as Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.