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

V Alesi, M L Dentici, S Loddo, S Genovese, V Orlando, C Calacci, D Pompili, B Dallapiccola, M C Digilio, A Novelli

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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.

Original languageEnglish
JournalAnnals of Human Genetics
DOIs
Publication statusE-pub ahead of print - Oct 10 2018

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Haploinsufficiency
De Lange Syndrome
Phenotype
Genes
Genetic Association Studies
Point Mutation
Intellectual Disability
Mutation

Cite this

@article{066140fef4824a14946bcc5240a4573c,
title = "Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange-like phenotype and delineation of a 19p13.12p13.11 gene contiguous syndrome",
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.",
author = "V Alesi and Dentici, {M L} and S Loddo and S Genovese and V Orlando and C Calacci and D Pompili and B Dallapiccola and Digilio, {M C} and A Novelli",
note = "{\circledC} 2018 John Wiley & Sons Ltd/University College London.",
year = "2018",
month = "10",
day = "10",
doi = "10.1111/ahg.12289",
language = "English",
journal = "Annals of Human Genetics",
issn = "0003-4800",
publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Confirmation of BRD4 haploinsufficiency role in Cornelia de Lange-like phenotype and delineation of a 19p13.12p13.11 gene contiguous syndrome

AU - Alesi, V

AU - Dentici, M L

AU - Loddo, S

AU - Genovese, S

AU - Orlando, V

AU - Calacci, C

AU - Pompili, D

AU - Dallapiccola, B

AU - Digilio, M C

AU - Novelli, A

N1 - © 2018 John Wiley & Sons Ltd/University College London.

PY - 2018/10/10

Y1 - 2018/10/10

N2 - 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.

AB - 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.

U2 - 10.1111/ahg.12289

DO - 10.1111/ahg.12289

M3 - Article

C2 - 30302754

JO - Annals of Human Genetics

JF - Annals of Human Genetics

SN - 0003-4800

ER -