000170395 001__ 170395
000170395 005__ 20260420103354.0
000170395 0247_ $$2doi$$a10.1038/s41467-026-71177-6
000170395 0248_ $$2sideral$$a148866
000170395 037__ $$aART-2026-148866
000170395 041__ $$aeng
000170395 100__ $$aParenti, Ilaria
000170395 245__ $$aPathogenic variants in the cohesin loader subunit MAU2 underlie a distinct Cornelia de Lange Syndrome subtype
000170395 260__ $$c2026
000170395 5060_ $$aAccess copy available to the general public$$fUnrestricted
000170395 5203_ $$aThe role of the cohesin complex depends on the cohesin loader proteins NIPBL and MAU2. While NIPBL variants are a major cause of Cornelia de Lange Syndrome (CdLS), the role of MAU2 in disease is unclear. We describe 18 individuals carrying 15 heterozygous MAU2 variants and demonstrate pathogenicity through functional analyses. In-frame MAU2 variants predominantly impair NIPBL–MAU2 interaction, whereas truncating variants cause MAU2 haploinsufficiency and lead to NIPBL reduction. Most individuals exhibit a DNA methylation profile compatible with the CdLS episignature. We also describe two MAU2-specific episignatures that reflect variant-dependent molecular consequences. Affected individuals display a wide range of phenotypes, from classic CdLS to milder presentations, with short stature and microcephaly as major features. A heterozygous Mau2 knockout mouse model recapitulates these traits, confirming the causal role of MAU2 disruption in vivo. Our study establishes MAU2 as a CdLS-associated gene and delineates a MAU2-related chromatinopathy with variable expressivity.
000170395 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/B32-20R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI23-01370
000170395 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000170395 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000170395 700__ $$aHesters, Alina
000170395 700__ $$0(orcid)0000-0001-6858-1575$$aGil-Salvador, Marta
000170395 700__ $$aDuffy, Laura
000170395 700__ $$aKanber, Deniz
000170395 700__ $$aBeygo, Jasmin
000170395 700__ $$aKerkhof, Jennifer
000170395 700__ $$aSteenpaß, Laura
000170395 700__ $$aLeitão, Elsa
000170395 700__ $$aWoestefeld, Julia
000170395 700__ $$aBoone, Philip M.
000170395 700__ $$aKao, Emeline M.
000170395 700__ $$aAlabdi, Lama
000170395 700__ $$aAldhalaan, Hesham M.
000170395 700__ $$aAlkuraya, Fowzan S.
000170395 700__ $$aAlshammari, Muneera J.
000170395 700__ $$aAntonarakis, Stylianos E.
000170395 700__ $$aBasel, Donald
000170395 700__ $$aCassinari, Kevin
000170395 700__ $$ade Polli Cellin, Laurana
000170395 700__ $$aClause, Amanda R.
000170395 700__ $$ade Lima Jorge, Alexander Augusto
000170395 700__ $$ade Castro Leal, Andréa
000170395 700__ $$aCollins, Stephan C.
000170395 700__ $$aDurand, Benjamin
000170395 700__ $$aEckhold, Juliane
000170395 700__ $$aHashem, Mais O.
000170395 700__ $$aJayakar, Parul
000170395 700__ $$aKhan, Arif O.
000170395 700__ $$aKato, Kohji
000170395 700__ $$aKubica, Regina
000170395 700__ $$aLyon, Gholson J.
000170395 700__ $$aMarchi, Elaine
000170395 700__ $$aMcCarrier, Julie
000170395 700__ $$aKimmig, Lara K.
000170395 700__ $$aMizuno, Seiji
000170395 700__ $$aNicolas, Gael
000170395 700__ $$aNishio, Yosuke
000170395 700__ $$aOgi, Tomoo
000170395 700__ $$aPié, Juan
000170395 700__ $$aPrell, Jordyn
000170395 700__ $$aPuisac, Beatriz
000170395 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, Feliciano J.$$uUniversidad de Zaragoza
000170395 700__ $$aRanza, Emmanuelle
000170395 700__ $$aRedin, Claire
000170395 700__ $$aRush, Eric
000170395 700__ $$aSaitoh, Shinji
000170395 700__ $$aShamseldin, Hanan E.
000170395 700__ $$aStarling, Susan
000170395 700__ $$aAstiazaran-Symonds, Esteban
000170395 700__ $$aEltahir, Sara H.
000170395 700__ $$aKuechler, Alma
000170395 700__ $$aSadikovic, Bekim
000170395 700__ $$aYalcin, Binnaz
000170395 700__ $$aWendt, Kerstin S.
000170395 700__ $$aKaiser, Frank J.
000170395 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000170395 773__ $$g17, 1 (2026)$$tNature communications$$x2041-1723
000170395 8564_ $$s6809155$$uhttps://zaguan.unizar.es/record/170395/files/texto_completo.pdf$$yVersión publicada
000170395 8564_ $$s2781652$$uhttps://zaguan.unizar.es/record/170395/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000170395 909CO $$ooai:zaguan.unizar.es:170395$$particulos$$pdriver
000170395 951__ $$a2026-04-18-10:48:45
000170395 980__ $$aARTICLE