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Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange–like phenotype and delineation of a 19p13.12p13.11 gene contiguous syndrome
Author(s) -
Alesi Viola,
Dentici Maria Lisa,
Loddo Sara,
Genovese Silvia,
Orlando Valeria,
Calacci Chiara,
Pompili Daniele,
Dallapiccola Bruno,
Digilio Maria Cristina,
Novelli Antonio
Publication year - 2019
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12289
Subject(s) - haploinsufficiency , phenotype , cornelia de lange syndrome , genetics , biology , gene , mutation , human genetics , genotype phenotype distinction , medicine
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.