MRC Institute of Genetics & Molecular Medicine
MRC Institute of Genetics & Molecular Medicine

Enhancer link to developmental disorders

A new genetic cause of Cornelia de Lange–like syndrome improves our understanding of how our genome controls our development: January 2018

super-enhancer link developmental disorder

Cornelia de Lange Syndrome (CdLS) is a very rare genetic disorder. It causes a range of physical, cognitive, and medical challenges. Research from the MRC Human Genetics Unit have linked a new series of genetic mutations to a group of disorders very similar to CdLS.

The mutations, to a gene called BRD4, affect the way that genes are controlled during the careful orchestration of embryonic and foetal development. Clues from previous mouse studies suggest that a reduced amount of BRD4 can lead to changes similar to those observed in human CdLS. The researchers discovered that the BRD4 protein can interact with another protein called NIPBL which is already known to be mutated in CdLS.

In this study, researchers looked for places where BRD4 and NIPBL appear to bind at the same DNA site. They found that many of these sites appeared in specialised areas of the genome called enhancers. These areas of DNA do not code for protein, but can change the control of other genes, altering the course of development.

Further studies are needed to better understand how BRD4 and NIPBL work together and how changes in these can lead to developmental disorders.



This work helps us diagnose children with CdLS quickly and accurately but will also provide focus for future research into the underlying developmental changes that cause these children so many different clinical problems

David FitzPatrick, Professor, MRC Human Genetics Unit at the University of EdinburghStudy senior author

The study was published in the journal Nature Genetics. 

Olley et al. BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome. Nature Genetics (2018) doi:10.1038/s41588-018-0042-y

  • BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome. Olley et al, Nature Genetics (2018) doi:10.1038/s41588-018-0042-y
  • David FitzPatrick Research Group