000148201 001__ 148201
000148201 005__ 20250923084439.0
000148201 0247_ $$2doi$$a10.3389/fgene.2024.1472543
000148201 0248_ $$2sideral$$a141687
000148201 037__ $$aART-2024-141687
000148201 041__ $$aeng
000148201 100__ $$aLucia-Campos, Cristina
000148201 245__ $$aAn intragenic duplication in the AFF2 gene associated with Cornelia de Lange syndrome phenotype
000148201 260__ $$c2024
000148201 5060_ $$aAccess copy available to the general public$$fUnrestricted
000148201 5203_ $$aCornelia de Lange syndrome (CdLS, OMIM #122470, #300590, #300882, #610759, and #614701) is a rare congenital disorder that affects the development of multiple organs and is characterized by physical abnormalities and cognitive and behavioral disabilities. Its molecular basis is mainly based on alterations in genes encoding structural and regulatory proteins related to the cohesin complex. Moreover, other transcriptional regulatory factors have been linked to this syndrome. However, additional causative genes are still unknown, since many patients still lack a molecular diagnosis. Herein, we describe a case with multiple affected family members presenting with an intragenic duplication in the AFF2 gene. The direct tandem intragenic duplication of exons 10, 11 and 12 was detected through high-resolution array Comparative Genomic Hybridization and next-generation sequencing technologies. Confirming the X-linked inheritance pattern, the duplication was found in the patient, his mother and his maternal aunt affected (dizygotic twins). Targeted sequencing with Oxford Nanopore Technologies revealed an aberrant transcript which is predominantly expressed in the patient and his aunt. Along with these results, a significant reduction in AFF2 gene expression levels was detected in these two individuals. Clinically both subjects exhibit a classic CdLS phenotype, whereas the mother is mostly unaffected. Consistent with the phenotypical differences observed between the mother and the aunt, there is a marked difference in X-inactivation patterns skewing. Given the crucial role of AFF2 in transcriptional regulation, it is not surprising that AFF2 variants can give rise to CdLS phenotypes. Therefore, the AFF2 gene should be considered for the molecular diagnosis of this syndrome.
000148201 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B32-23R$$9info:eu-repo/grantAgreement/ES/ISCIII/FI20-00290$$9info:eu-repo/grantAgreement/ES/ISCIII/PI19-01860$$9info:eu-repo/grantAgreement/ES/ISCIII/PI23-01370
000148201 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000148201 590__ $$a2.8$$b2024
000148201 592__ $$a0.863$$b2024
000148201 591__ $$aGENETICS & HEREDITY$$b79 / 191 = 0.414$$c2024$$dQ2$$eT2
000148201 593__ $$aGenetics$$c2024$$dQ2
000148201 593__ $$aMolecular Medicine$$c2024$$dQ2
000148201 593__ $$aGenetics (clinical)$$c2024$$dQ2
000148201 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000148201 700__ $$aParenti, Ilaria
000148201 700__ $$0(orcid)0000-0002-4703-6620$$aLatorre-Pellicer, Ana$$uUniversidad de Zaragoza
000148201 700__ $$0(orcid)0000-0001-6858-1575$$aGil-Salvador, Marta$$uUniversidad de Zaragoza
000148201 700__ $$aBestetti, Ilaria
000148201 700__ $$aFinelli, Palma
000148201 700__ $$aLarizza, Lidia
000148201 700__ $$0(orcid)0000-0001-9962-2157$$aArnedo, María$$uUniversidad de Zaragoza
000148201 700__ $$0(orcid)0000-0002-0023-8137$$aAyerza-Casas, Ariadna$$uUniversidad de Zaragoza
000148201 700__ $$aDel Rincón, Julia
000148201 700__ $$aTrujillano, Laura
000148201 700__ $$aMorte, Beatriz
000148201 700__ $$aPérez-Jurado, Luis A.
000148201 700__ $$aLapunzina, Pablo
000148201 700__ $$aLeitão, Elsa
000148201 700__ $$aBeygo, Jasmin
000148201 700__ $$aLich, Christina
000148201 700__ $$aKilpert, Fabian
000148201 700__ $$aKaya, Sabine
000148201 700__ $$aDepienne, Christel
000148201 700__ $$aKaiser, Frank J.
000148201 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, Feliciano J.$$uUniversidad de Zaragoza
000148201 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, Beatriz$$uUniversidad de Zaragoza
000148201 700__ $$0(orcid)0000-0003-3203-6254$$aPié, Juan$$uUniversidad de Zaragoza
000148201 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000148201 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000148201 773__ $$g15 (2024), [15 pp.]$$pFront. genet.$$tFrontiers in Genetics$$x1664-8021
000148201 8564_ $$s2649737$$uhttps://zaguan.unizar.es/record/148201/files/texto_completo.pdf$$yVersión publicada
000148201 8564_ $$s2401244$$uhttps://zaguan.unizar.es/record/148201/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000148201 909CO $$ooai:zaguan.unizar.es:148201$$particulos$$pdriver
000148201 951__ $$a2025-09-22-14:49:41
000148201 980__ $$aARTICLE