Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Volume 182, Issue 7, Pages 1690-1696Publisher
WILEY
DOI: 10.1002/ajmg.a.61611
Keywords
chromatin remodeling; Cornelia de Lange syndrome; KBG syndrome; Rubinstein-Taybi syndrome; transcription
Categories
Funding
- Diputacion General de Aragon [B32_17R]
- Fondazione Pisa [120/16]
- Spanish Ministry of Health - Fondo de Investigacion Sanitaria [PI19/01860]
Ask authors/readers for more resources
Cornelia de Lange syndrome (CdLS), Rubinstein-Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS-like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available