Bellvitge University Hospital and Bellvitge Biomedical Research Institute (IDIBELL) have identified a hitherto undescribed recurrent chromosomal abnormality that explains cases of hereditary hemorrhagic telangiecstasy (HHT), also known as Rendu-Osler disease. The finding allows us to respond to families who had been living with the disease for years without knowing its genetic cause.
Rendu-Osler disease is a rare inherited vascular disease that can lead to daily nosebleeds, chronic anemia, and vascular malformations in the lungs, liver, or brain that can lead to potentially serious complications.
The research, published in the European Journal of Internal Medicine, has been led by professionals from the HHT Unit of the Bellvitge University Hospital, the largest in Spain, with nearly 500 people treated, in collaboration with professionals from the Hospital Clínic de Barcelona.
Why is it important to know the genetic cause?
When a person has Rendu-Osler disease, identifying the genetic cause allows other family members who may have inherited it even if they have no obvious symptoms. This facilitates the early detection of possible complications and allows appropriate medical follow-up to be initiated before health problems appear.
“For many families, naming the genetic cause of the disease means ending years of uncertainty. In addition, it allows us to identify family members at risk and act before potentially serious complications appear,” explains Anna Esteve-Garcia, genetic advisor at Bellvitge University Hospital, IDIBELL researcher and first author of the study.
In a hereditary disease such as HHT, early detection of affected people allows specific studies to be carried out to identify vascular malformations in the lungs, liver or brain before they cause serious complications.
An unexpected clue: a history of repeated miscarriages
Most people with Rendu-Osler disease have a known genetic alteration. However, between 15% and 20% still do not know which genetic alteration is responsible for their disease.
This was the case for the four families included in the study. Despite meeting international clinical diagnostic criteria, genetic analyses carried out over the years had not identified the cause. One element particularly caught the attention of the research team: all the families shared a history of repeated miscarriages.
This observation led the professionals to review previous chromosomal studies and delve into the genetic analysis of the cases. The research ended up identifying a recurrent chromosomal alteration that affected chromosomes 9 and 12 and altered the functioning of the ACVRL1 gene, one of the main genes related to Rendu-Osler disease.
The particularity of this alteration is that it can go unnoticed with the usual strategies of exome sequencing, one of the most widely used tools today to diagnose hereditary diseases.
“The finding highlights the importance of incorporating new analysis strategies, since certain pathological variants can go undetected with the usual sequencing techniques. Based on these cases, we have incorporated analysis tools that facilitate the detection of this translocation from whole exome data, thus expanding the diagnostic performance of a test that is already part of routine clinical practice and increasing the diagnostic capacity in complex rare diseases”, highlights Dr Ariadna Padró-Miquel, a specialist in the Molecular Genetics Area of the Clinical Laboratory of the Bellvitge University Hospital and senior author of the study.
Bellvitge, an international benchmark in Rendu-Osler disease
This finding consolidates a line of research that in recent months has placed Bellvitge among the international reference centers in Rendu-Osler disease.
At the end of 2025, professionals from the same unit participated in the study published in The New England Journal of Medicine that demonstrated the efficacy of the first treatment developed specifically for this disease.
“In just a few months we have contributed to two very important advances for the international community of people with HHT: the demonstration of the first disease-specific treatment and now the identification of a new genetic mechanism. This reflects the strength of a multidisciplinary model that integrates care, diagnosis and research, as well as the role of IDIBELL’s REMMA programme in transforming research into real benefits for people with rare diseases”, says Dr Antoni Riera-Mestre, head of the Internal Medicine Service at Bellvitge University Hospital, head of the HHT Unit and head of the Systemic, Vascular Diseases and Aging of IDIBELL.
“In rare diseases such as HHT, reaching the correct diagnosis is not only a matter of scientific knowledge. It can change the medical follow-up of an entire family and allow affected people to be detected before they develop complications,” adds Dr. Riera-Mestre.
This new finding expands knowledge about the genetic causes of Rendu-Osler disease and opens the door to diagnosing cases that until now had no genetic explanation.
About Bellvitge University Hospital
Bellvitge Hospital is a public, university, research and innovative hospital. With more than 5,200 expert and committed professionals, it is the local hospital for the citizens of L’Hospitalet and El Prat de Llobregat and a reference centre of maximum complexity for 2 million people, the entire southern axis of Catalonia. It is the Catalan health centre that performs the most complex surgery, especially oncological surgery, and is part of the Bellvitge Health Campus, recognised by the Organisation of European Cancer Institutes (OECI) as a Comprehensive Cancer Centre for its excellence in cancer care, research and teaching. It integrates in the projects the orientation to improve the patient experience and networking with primary care and the surrounding hospitals. Oriented towards personalised medicine, it has the best genetic diagnosis and imaging tools for cancer and rare diseases, which are complemented by the High Precision Diagnostic Centre, which has the first PET/Magnetic Resonance Imaging in the healthcare network in Spain. It registers about 26,000 major surgery interventions annually; 39,000 discharges; 400,000 outpatient visits and about 100,000 diagnostic tests.
About IDIBELL
The Bellvitge Biomedical Research Institute (IDIBELL) is a research centre created in 2004 and specialising in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from 73 research groups, publish more than 1,400 scientific articles a year. L’IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Health Institute, 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 d’Excelencia Internacional 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 centres 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 Centre of the AECC Scientific Foundation (FCAECC).