Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange–like phenotype and delineation of a 19p13.12p13.11 gene contiguous syndrome. (10th October 2018)

• Record Type: Journal Article
• Authors: Alesi, Viola; Dentici, Maria Lisa; Loddo, Sara; Genovese, Silvia; Orlando, Valeria; Calacci, Chiara; Pompili, Daniele; Dallapiccola, Bruno; Digilio, Maria Cristina; Novelli, Antonio
• Is Part Of: Annals of human genetics. Volume 83:Number 2(2019:Mar.)
• Page Start: 100
• Page End: 109
• Publication Date: 2018-10-10
• Subjects: 19p interstitial deletion -- 19p13 -- BRD4 -- Cornelia de Lange; Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12289
• Languages: English
• ISSNs: 0003-4800

Abstract

Abstract: Cornelia de Lange syndrome (CdLS) is a genetically and clinical heterogeneous condition characterized by congenital malformation, intellectual disability, and peculiar dysmorphic features. Recently, BRD4 (19p13.12) was proposed as a new critical gene associated with a mild CdLS because of a similar presentation of the patients carrying point mutations and of its involvement in the NIPBL pathway. Patients harboring a 19p interstitial deletion shared some physical features with BRD4 mutation carriers, which results in a more complex phenotype because of the involvement of several neighboring genes. We report a new 19p deletion in a patient clinically diagnosed as CdLS, partially overlapping with previously published cases with the aim to support the role of BRD4 haploinsufficiency in a CdL‐like phenotype and to improve the delineation of 19p13.12p13.11 deletion as a new nonrecurrent gene contiguous syndrome, spanning GIPC1, NOTCH3, BRD4, AKAP8, AKAP8L, CASP14, and EPS15L1 genes. Previously described cases are reviewed, attempting to delineate a genotype–phenotype correlation.