Identified key alteration in the genes involved in the development of Cornelia de Lange syndrome

A study identifies the molecular basis of this rare disease, which causes extremities abnormalities and growth delay.
The scientific team manages to reverse some effects of the disease through gene therapy in patients’ cultured cells.

A study carried out at IDIBELL, led by a research group from IBV-CSIC, published in Nature Communications reveals the molecular bases of Cornelia de Lange syndrome, a rare disease that affects development during pregnancy and causes abnormalities in the upper extremities, growth delay, psychomotor alterations, and intellectual disability, among other symptoms. The study identifies a key alteration in the function of a set of proteins that causes problems in DNA compaction.

“Most Cornelia de Lange patients present a mutation in genes of the protein complex called cohesin or its regulators, responsible for maintaining the structure of chromosomes. Our objective was to study how mutations in these genes cause the disease”, says Ethel Queralt, scientist of the Gen-T Plan of the Generalitat Valenciana at the IBV-CSIC, who leads the study. “In this study, we have observed that the cohesins and DNA binding is altered in Cornelia de Lange patients. We think this causes problems in DNA compaction. Thus, the disfunction of cohesin in DNA folding causes alterations in gene expression that give rise to the disease”, reveals the researcher.

Thanks to the knowledge acquired in this work, the team of researchers has tested a possible therapy. “We have introduced an unaltered gene into patient cultured cells, and these new genes have been able to reverse most of the observed gene expression defects, suggesting that a gene therapy could work in patients,” says Dr. Queralt.

The University of Zaragoza, the National Center for Oncological Research (CNIO), the Instituto de Investigación Sanitaria de la Fe, the Josep Carreras Leukemia Research Institute (IJC), and the company Qgenomics also participate in the study.

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).