000119825 001__ 119825
000119825 005__ 20240319081005.0
000119825 0247_ $$2doi$$a10.3390/genes13081413
000119825 0248_ $$2sideral$$a130670
000119825 037__ $$aART-2022-130670
000119825 041__ $$aeng
000119825 100__ $$aLucia-Campos, Cristina
000119825 245__ $$aA Novel Intragenic Duplication in the HDAC8 Gene Underlying a Case of Cornelia de Lange Syndrome
000119825 260__ $$c2022
000119825 5060_ $$aAccess copy available to the general public$$fUnrestricted
000119825 5203_ $$aCornelia de Lange syndrome (CdLS) is a multisystemic genetic disorder characterized by distinctive facial features, growth retardation, and intellectual disability, as well as various systemic conditions. It is caused by genetic variants in genes related to the cohesin complex. Single-nucleotide variations are the best-known genetic cause of CdLS; however, copy number variants (CNVs) clearly underlie a substantial proportion of cases of the syndrome. The NIPBL gene was thought to be the locus within which clinically relevant CNVs contributed to CdLS. However, in the last few years, pathogenic CNVs have been identified in other genes such as HDAC8, RAD21, and SMC1A. Here, we studied an affected girl presenting with a classic CdLS phenotype heterozygous for a de novo ~32 kbp intragenic duplication affecting exon 10 of HDAC8. Molecular analyses revealed an alteration in the physiological splicing that included a 96 bp insertion between exons 9 and 10 of the main transcript of HDAC8. The aberrant transcript was predicted to generate a truncated protein whose accessibility to the active center was restricted, showing reduced ease of substrate entry into the mutated enzyme. Lastly, we conclude that the duplication is responsible for the patient’s phenotype, highlighting the contribution of CNVs as a molecular cause underlying CdLS.
000119825 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B32-17R$$9info:eu-repo/grantAgreement/ES/DGA/B32-20R$$9info:eu-repo/grantAgreement/ES/FIS/PI19-01860
000119825 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000119825 590__ $$a3.5$$b2022
000119825 592__ $$a0.924$$b2022
000119825 591__ $$aGENETICS & HEREDITY$$b66 / 171 = 0.386$$c2022$$dQ2$$eT2
000119825 593__ $$aGenetics (clinical)$$c2022$$dQ2
000119825 593__ $$aGenetics$$c2022$$dQ2
000119825 594__ $$a5.1$$b2022
000119825 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000119825 700__ $$aValenzuela, Irene
000119825 700__ $$0(orcid)0000-0002-4703-6620$$aLatorre-Pellicer, Ana$$uUniversidad de Zaragoza
000119825 700__ $$aRos-Pardo, David
000119825 700__ $$0(orcid)0000-0001-6858-1575$$aGil-Salvador, Marta$$uUniversidad de Zaragoza
000119825 700__ $$0(orcid)0000-0001-9962-2157$$aArnedo, María$$uUniversidad de Zaragoza
000119825 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, Beatriz$$uUniversidad de Zaragoza
000119825 700__ $$aCastells, Neus
000119825 700__ $$aPlaja, Alberto
000119825 700__ $$aTenes, Anna
000119825 700__ $$aCuscó, Ivon
000119825 700__ $$aTrujillano, Laura
000119825 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, Feliciano J.$$uUniversidad de Zaragoza
000119825 700__ $$aTizzano, Eduardo F.
000119825 700__ $$aGómez-Puertas, Paulino
000119825 700__ $$0(orcid)0000-0003-3203-6254$$aPié, Juan$$uUniversidad de Zaragoza
000119825 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000119825 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000119825 773__ $$g13, 8 (2022), 1413 [11 pp.]$$pGenes (Basel)$$tGenes$$x2073-4425
000119825 8564_ $$s1448603$$uhttps://zaguan.unizar.es/record/119825/files/texto_completo.pdf$$yVersión publicada
000119825 8564_ $$s2790397$$uhttps://zaguan.unizar.es/record/119825/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000119825 909CO $$ooai:zaguan.unizar.es:119825$$particulos$$pdriver
000119825 951__ $$a2024-03-18-14:32:03
000119825 980__ $$aARTICLE