Undiagnosed Rare Diseases Programme (ENoD)

The Program for Undiagnosed Rare diseases, EnoD, is an initiative of CIBERER aimed at improving knowledge about the genetic causes of rare diseases. It entails the discovery of new genes and variants. It is effective through the study of specific clinical cases without molecular diagnostics. To this end, ENoD program places research directly at the service of the National Health System.

ENoD is framed in one of the priority international lines (IRDIRC, H2020) as it is the identification of the genetic causes of rare diseases.

It is a transversal and collaborative program counting on the participation of many Consortium groups.

Context and needs of the program

Over 80% of rare diseases have a genetic cause. Achievement of a genetic diagnosis is essential for the correct management of these patients and in order to provide genetic counselling to their families. The reality is that there are many clinical cases that have not identified the molecular origin of the disease (approx. 30%) after applying the established diagnostic protocols.

This is due to the great complexity of these pathologies:

New diseases and new genes associated with known diseases are constantly been described.
Multisystem involvement and overlapping with other pathologies which sometimes makes them difficult to diagnose.
The difficulty of interpretation of new massive sequencing techniques.

These undiagnosed patients represent an unsolved need, located on the frontier of the translational process between research and the clinical practice. For its correct diagnosis, they need a deep and up-to-date knowledge of pathologies or application of latest techniques. Thus, the Undiagnosed Rare diseases program, ENoD of CIBERER aims to become an important diagnostic resource at the service of everyone.

Objective

To contribute to the precise molecular diagnosis of unsolved clinical cases once the proper (rutinary) care procedures have been exhausted.
If necessary, search for new genomic alterations not described so far as the cause of disease.

What does the program offer?

With a structure based on transversal committees and endowed with its own resources, it manages undiagnosed cases referred by CIBERER research groups with the following purposes:

DIAGNOSTIC ORIENTATION AND EXPERT ADVICE
If there are previous genomic tests, a reinterpretation of these complex data is offered by our Bioinformatics´ infrastructure.
REINTERPRETATION OF PREVIOUS GENOMIC DATA
Si existieran pruebas genómicas previas, se ofrece una reinterpretación de estos datos complejos gracias a la infraestructura en Bioinformática de la que disponemos.
MASSIVE SEQUENCING TECHNIQUES
Finally, a Committee selects those cases remaining unsolved. The search for new genes associated with the disease through the use of sequencing techniques (Exome, genome and transcriptome) is initiated. These studies are financially supported by CIBERER’s own budget, as well as their subsequent bioinformatics analysis.

In addition, an agreement has been signed with FEDER, through their Orientation and Information Service, SIO, aimed at collaboration to unravel diagnosis of unsolved clinical cases.

History of the program

Numerous CIBERER groups are active agents in diagnostics, as evidenced by their scientific production.
Since 2011, CIBERER has coordinated strategic actions with the aim of discovering new genes and variants involved in the etiology of rare diseases to ultimately contribute to the accurate molecular diagnosis of unsolved clinical cases. As a result of this program, many positive results have been obtained and many unknowns have been solved.
In 2015, we took a step forward by launching the Program for Undiagnosed Rare Diseases, ENoD, which provides a new structure and reinforces the commitment to this strategic objective. It started with a pilot study that included a total of 200 patients enrolled in the CIBERER intramural project "Characterization and contribution to the genetic diagnosis in a cohort of patients with intellectual disabilities, autism or epilepsy".
Currently, the ENoD program is open to all rare genetic diseases, studying individual cases (not necessarily belonging to a patient cohort).
As a result of these initiatives, a total of 88 new genes and variants associated to rare diseases have been discovered in the 2011-2018 period.

ENoD team

Coordinator: Dr. Luis Pérez Jurado (Miembro del Comité de Dirección del CIBERER)
Clinical and Executive Committee: 12 members of the CIBERER with a clinical and genetics background.
Project Manager: Dra. Beatriz Morte Contact email: [email protected]