Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange–like phenotype and delineation of a 19p13.12p13.11 gene contiguous syndrome

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...

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Bibliographic Details
Published in:Annals of human genetics 2019-03, Vol.83 (2), p.100-109
Main Authors: Alesi, Viola, Dentici, Maria Lisa, Loddo, Sara, Genovese, Silvia, Orlando, Valeria, Calacci, Chiara, Pompili, Daniele, Dallapiccola, Bruno, Digilio, Maria Cristina, Novelli, Antonio
Format: Article
Language:English
Subjects:
19p interstitial deletion
19p13
BRD4
Cell Cycle Proteins - genetics
Child, Preschool
Chromosome 12
Chromosome 19
Chromosome Deletion
Chromosomes, Human, Pair 19
Congenital defects
Cornelia de Lange
De Lange syndrome
De Lange Syndrome - genetics
Female
Gene deletion
Genes
Genotype & phenotype
Genotypes
Haploinsufficiency
Humans
Infant
Infant, Newborn
Mutation
Phenotype
Phenotypes
Transcription Factors - genetics
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Summary: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.
ISSN:0003-4800
1469-1809
DOI:10.1111/ahg.12289