The Clinical Genomics research group is part of the Genetics Department at Germans Trias Hospital in the North Metropolitan Area of Barcelona (LCMN). The group has several important responsibilities, including diagnosing and monitoring patients with hereditary diseases, providing genetic counseling to patients and their families, and conducting genetic tests to determine the genetic cause of these diseases. This research group is dedicated to improving patient management by considering all aspects of patient care, including emotional, social, religious, and physical dimensions.

Their members are also focused on increasing the cost-effectiveness of genetic testing and enhancing their knowledge of the genetic bases of various diseases. To achieve this goal, they are actively developing new genomic techniques to analyze germline and somatic variants at both RNA and DNA levels. Additionally, they are participating in the development of new methodologies to determine the status of known pharmacogenomics biomarkers and to detect SARS-COV-2.

Furthermore, the group is a member of the Spanish Reference Center (CSUR) for adult patients with Phakomatoses (Neurofibromatoses, Schwannomatosis, Tuberous Sclerosis, and Von-Hippel Lindau diseases), which is a part of the European Network of Reference Centers (ERN) GENTURIS. The team is working on developing personalized medicine for this group of patients and developing new clinical guidelines that also take into account patients' emotional and social needs. They are also discovering new prognostic biomarkers, understanding the role of genomic alterations in the development of disease-associated lesions, and implementing various gene therapy strategies to cure these diseases.

Keywords: Neurofibromatosis type 2, clinical genomics, gene therapy, schwannomas, genetic testing.

Clinical Genomics Research

Research lines

Management of phakomatoses patients

Improving the management of phakomatoses patients considering not only clinical diagnosis but also emotional, social, religious and physical dimensions that could impact patients with these rare diseases.

Development and implementation of new genomic techniques for genetic diagnosis of hereditary diseases

Increasing the cost-effectiveness of genetic testing and our knowledge of the genetic basis of some hereditary diseases (mostly phakomatoses and hereditary renal diseases). The group is focusing research on developing new genomic techniques, both at RNA and DNA levels, to analyse both germline and somatic variants.

Personalised medicine for neurofibromatoses

Developing personalised medicine for neurofibromatoses and schwannomatosis patients, which include the discovery of new prognostic biomarkers, understanding the role of patient's genomic alterations in the development of disease-associated lesions and the implementation of different gene therapy strategies as a potential treatment for this group of diseases.

Genetic susceptibility to illness

Developing strategies to evaluate genetic individual susceptibility to illness. This will allow for the implementation of personalised and precision medicine in different areas of the Can Ruti campus.

Active projects

EURONET- NF: European Network for improved molecular diagnostics of the NeuroFibromatoses - schwannomatoses and related disorders

PI: Elisabeth Castellanos
Funding agency: European Joint Program for Rare Diseases (EJP -RD) a través de "Proyectos de colaboración internacional" del Instituto de Salud Carlos III (AC22/00033)
Agency code: EJPRD22-084
Start date: 01/06/2023
End date: 31/05/2026

Developing NF2 iPSC-cell models for the use of antisense oligonucleotides as a personalized therapy for Neurofibromatosis Type 2 patients

PI: Elisabeth Castellanos
Funding agency: Children's Tumor Foundation
Agency code: CTF-2022-05-005
Start date: 01/02/2023
End date: 31/01/2024

Suppression of NF1 Nonsense Mutations by RNA-guided RNA Pseudouridylation

PI: Elisabeth Castellanos, Yi Tao, Conxi Lazaro, Pedro Marais
Funding agency: Gilbert Family Foundation
Start date: 01/01/2022
End date: 31/12/2024

Plataforma de medicina de precisió, una eina necessària per la transformació del procés assistencial

PI: Ignacio Blanco
Funding agency: HUGTP
Start date: 01/01/2023
End date: 31/12/2026

The human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection: Towards personalised medicine

PI: UNDINE Consortium; Collaborator: Ignacio Blanco
Funding agency: Horizon Europe
Start date: 01/09/2022
End date: 31/12/2026

Consolidation of WGS and RT-PCR activities for SARS-CoV-2 in Spain towards sustainable use and integration of enhanced infrastructure and processes in the RELECOV network

PI: Inmaculada Casas; Collaborator: Ignacio Blanco
Start date: 01/01/2023
End date: 31/12/2026

Genomic epidemiology of SARS-CoV-2 in Catalonia: virological vigilance and control of outbreaks

PI: Marc Noguera Julián, Elisa Martró Català
Agency code: 1162/U/2021
Start date: 01/06/2021
End date: 31/05/2024

A patient centered research: awareness of patientsneeds, clinical phenotyping and molecular pathogenesis in Neurofibromatosis type 2

PI: Elisabeth Castellanos
Funding agency: Fundació La Marató de TV3
Agency code: P126/C/2020
Start date: 01/04/2021
End date: 31/03/2024

Desarrollo de una estrategia de medicina personalizada para la NF2: mejora del diagnóstico genético, la evaluación de la calidad de vida y generación de un modelo de schwannomas a partir de iPSCs

PI: Elisabeth Castellanos, Ignacio Blanco
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI20/00215
Start date: 01/01/2021
End date: 31/12/2023

NF Variant Curation Expert Panel (VCEP)

PI: Elisabeth Castellanos
Funding agency: National Institutes of Health (NIH) ClinGen Variant Curation Expert Panel (VCEP)
Start date: 27/12/2021
End date: 30/12/2023

Programa de Ciencia de Datos (IMPaCT-Data), Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología (IMPaCT)

PI: Alfonso Valencia Herrera
Funding agency: Alliance for Education Solutions (AES)
Agency code: PI20/00215
Start date: 01/01/2021
End date: 31/12/2023

Scientific publications

Carrió M, Mazuelas H, Richaud-Patin Y, Gel B, Terribas E, Rosas I, Jimenez-Delgado S, Biayna J, Vendredy L, Blanco I, Castellanos E, Lázaro C, Raya Á, Serra E. Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas. Stem Cell Reports. 2019 Feb 12;12(2):411-426. DOI: 10.1016/j.stemcr.2019.01.001. Erratum in: Stem Cell Reports. 2019 Mar 5;12(3):639-641. PMID: 30713041; PMCID: PMC6373434.

Piotrowski A, Koczkowska M, Poplawski AB, Bartoszewski R, Króliczewski J, Mieczkowska A, Gomes A, Crowley MR, Crossman DK, Chen Y, Lao P, Serra E, Llach MC, Castellanos E, Messiaen LM. Targeted massively parallel sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas: An analysis of 51 individuals in a single-center experience. Hum Mutat. 2022 Jan;43(1):74-84. DOI: 10.1002/humu.24294. Nov 15. PMID: 34747535.

Evans DG, Mostaccioli S, Pang D, Fadzil O Connor M, Pittara M, Champollion N, Wolkenstein P, Thomas N, Ferner RE, Kalamarides M, Peyre M, Papi L, Legius E, Becerra JL, King A, Duff C, Stivaros S, Blanco I. ERN GENTURIS clinical practice guidelines for the diagnosis, treatment, management and surveillance of people with schwannomatosis. Eur J Hum Genet. 2022 Jul;30(7):812-817. DOI: 10.1038/s41431-022-01086-x. PMID: 35361920; PMCID: PMC9259735.

International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC); Huson SM, Wolkenstein P, Evans DG. Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation. Genet Med. 2022 Sep;24(9):1967-1977. DOI: 10.1016/j.gim.2022.05.007. PMID: 35674741.

Mazuelas H, Magallón-Lorenz M, Fernández-Rodríguez J, Uriarte-Arrazola I, Richaud-Patin Y, Terribas E, Villanueva A, Castellanos E, Blanco I, Raya Á, Chojnacki J, Heyn H, Romagosa C, Lázaro C, Gel B, Carrió M, Serra E. Modeling iPSC-derived human neurofibroma-like tumors in mice uncovers the heterogeneity of Schwann cells within plexiform neurofibromas. Cell Rep. 2022 Feb 15;38(7):110385. DOI: 10.1016/j.celrep.2022.110385. PMID: 35172160.

Catasús N, Garcia B, Galván-Femenía I, Plana A, Negro A, Rosas I, Ros A, Amilibia E, Becerra JL, Hostalot C, Rocaribas F, Bielsa I, Lazaro Garcia C, de Cid R, Serra E, Blanco I, Castellanos E; NF2 Spanish National Reference Centre HUGTP-ICO-IGTP. Revisiting the UK Genetic Severity Score for NF2: a proposal for the addition of a functional genetic component. J Med Genet. 2022 Jul;59(7):678-686. DOI: 10.1136/jmedgenet-2020-107548. PMID: 34348961.

Plana-Pla A, García B, Munera-Campos M, Catasus N, Serra Arenas E, Blanco I, Castellanos Perez E, Bielsa I; NF2 Multidisciplinary Clinics HUGTiP-ICO-IGTP. Skin lesions in neurofibromatosis type 2: diagnostic and prognostic significance of cutaneous (plexiform) schwannomas. J Eur Acad Dermatol Venereol. 2022 Sep;36(9):1632-1640. DOI: 10.1111/jdv.18190. PMID: 35490384; PMCID: PMC9543204.

Garcia B, Catasus N, Ros A, Rosas I, Negro A, Guerrero-Murillo M, Valero AM, Duat-Rodriguez A, Becerra JL, Bonache S, Lázaro Garcia C, Comas C, Bielsa I, Serra E, Hernández-Chico C, Martin Y, Castellanos E, Blanco I. Neurofibromatosis type 1 families with first-degree relatives harbouring distinct NF1 pathogenic variants. Genetic counselling and familial diagnosis: what should be offered? J Med Genet. 2022 Oct;59(10):1017-1023. DOI: 10.1136/jmedgenet-2021-108301. PMID: 35121649.

Catasús N, Rosas I, Bonache S, Negro A, Torres-Martin M, Plana-Pla A, Salvador H, Serra E, Blanco I, Castellanos E; NF2-related SWN Spanish National Reference Centre HUGTP-ICO-IGTP. Antisense oligonucleotides targeting exon 11 are able to partially rescue the NF2-related schwannomatosis phenotype in vitro. Mol Ther Nucleic Acids. 2022 Nov 4;30:493-505. DOI: 10.1016/j.omtn.2022.10.026. PMID: 36420221; PMCID: PMC9678674.

Bordoy AE, Saludes V, Panisello Yagüe D, Clarà G, Soler L, Paris de León A, Casañ C, Blanco-Suárez A, Guerrero-Murillo M, Rodríguez-Ponga B, Noguera-Julian M, Català-Moll F, Pey I, Armengol MP, Casadellà M, Parera M, Pluvinet R, Sumoy L, Clotet B, Giménez M, Martró E, Cardona PJ, Blanco I. Monitoring SARS-CoV-2 variant transitions using differences in diagnostic cycle threshold values of target genes. Sci Rep. 2022 Dec 17;12(1):21818. DOI: 10.1038/s41598-022-25719-9. PMID: 36528712; PMCID: PMC9758454.

publications of the group


Can Ruti celebra la jornada de malalties minoritàries denotant la importància de la recerca per ajudar als pacients

El dijous de la setmana passada, 29 de febrer, es va celebrar la 'Jornada dia internacional malalties minoritàries' a la sala d'actes de l'Hospital Germans Trias. Professionals de la salut i investigadors de l'Hospital i l'IGTP van explicar els seu treball per avançar en l'àmbit de les malalties minoritàries. També van intervenir representants d'associacions de pacients d'aquestes malalties.

- Recerca, Projectes

L’IGTP coordinarà un projecte europeu per millorar el diagnòstic i el tractament de les neurofibromatosis

Investigadors del grup de Genòmica Clínica de l'Institut de Recerca Germans Trias i Pujol (IGTP) i del Servei de Genètica de l'Hospital Germans Trias (HUGTiP), coordinaran el projecte EURONET-NF que té com a objectiu millorar el diagnòstic genètic dels pacients amb neurofibromatosis i schwannomatosis (NF-SWN). El projecte involucra a 6 països i ha estat finançat per la Unió Europea amb aproximadament 1.6 milions d'euros per als pròxims 3 anys.

+ Notícies