000089267 001__ 89267
000089267 005__ 20210902121628.0
000089267 0247_ $$2doi$$a10.1007/s00439-020-02138-2
000089267 0248_ $$2sideral$$a117520
000089267 037__ $$aART-2020-117520
000089267 041__ $$aeng
000089267 100__ $$aKrab, L.C.
000089267 245__ $$aDelineation of phenotypes and genotypes related to cohesin structural protein RAD21
000089267 260__ $$c2020
000089267 5060_ $$aAccess copy available to the general public$$fUnrestricted
000089267 5203_ $$aRAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype-phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype-phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.
000089267 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B32-17R$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00707$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094434-B-100$$9info:eu-repo/grantAgreement/ES/MINECO/RTC-2017-6494-1
000089267 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000089267 590__ $$a4.132$$b2020
000089267 591__ $$aGENETICS & HEREDITY$$b63 / 175 = 0.36$$c2020$$dQ2$$eT2
000089267 592__ $$a2.351$$b2020
000089267 593__ $$aGenetics (clinical)$$c2020$$dQ1
000089267 593__ $$aGenetics$$c2020$$dQ1
000089267 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000089267 700__ $$aMarcos-Alcalde, I.
000089267 700__ $$aAssaf, M.
000089267 700__ $$aBalasubramanian, M.
000089267 700__ $$aAndersen, J.B.
000089267 700__ $$aBisgaard, A.M.
000089267 700__ $$aFitzpatrick, D.R.
000089267 700__ $$aGudmundsson, S.
000089267 700__ $$aHuisman, S.A.
000089267 700__ $$aKalayci, T.
000089267 700__ $$aMaas, S.M.
000089267 700__ $$aMartinez, F.
000089267 700__ $$aMcKee, S.
000089267 700__ $$aMenke, L.A.
000089267 700__ $$aMulder, P.A.
000089267 700__ $$aMurch, O.D.
000089267 700__ $$aParker, M.
000089267 700__ $$0(orcid)0000-0003-3203-6254$$aPie, J.$$uUniversidad de Zaragoza
000089267 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, F.J.$$uUniversidad de Zaragoza
000089267 700__ $$aRieubland, C.
000089267 700__ $$aMokry, J.A.R.
000089267 700__ $$aScarano, E.
000089267 700__ $$aShinawi, M.
000089267 700__ $$aGomez-Puertas, P.
000089267 700__ $$aTumer, Z.
000089267 700__ $$aHennekam, R.C.
000089267 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000089267 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000089267 773__ $$g139 (2020), 575–592$$pHum. genet.$$tHUMAN GENETICS$$x0340-6717
000089267 8564_ $$s1365401$$uhttps://zaguan.unizar.es/record/89267/files/texto_completo.pdf$$yVersión publicada
000089267 8564_ $$s29128$$uhttps://zaguan.unizar.es/record/89267/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000089267 909CO $$ooai:zaguan.unizar.es:89267$$particulos$$pdriver
000089267 951__ $$a2021-09-02-08:51:19
000089267 980__ $$aARTICLE