In Argentina, where genetic testing is not affordable for most, this project will provide an accurate genetic diagnosis and genetic counselling for people with EBS. This means better prediction of the impact on a person's life by highlighting how different genetic changes cause different EBS symptoms.

 

Around 145 patients at the CEDIGEA clinic in Argentina will provide information about their EBS symptoms and give a small blood sample for DNA extraction and sequencing. Where genetic changes that cause EB are found, they will receive a genetic diagnosis free of charge in a country where this is not affordable for most. Their parents will be offered sequencing to confirm the diagnosis and genetic counselling specific to the family's genetic change. This research group previously published their sequencing results and associated symptoms for 181 people with DEB. This project will allow them to do the same for people living with EBS and contribute to filling the gap on genetic information from ethnically diverse populations.

Read more in our researcher's blog. 

 

Contents:

• Project summary (top of page)
• About our funding
• Latest progress summary (2024)
• About our researchers
• Why this research is important
• Researcher's abstract
• Researcher's progress update (2024)

 

About our funding:

 

Research leader	Dr Laura Valinotto
Institution	Centre for Research in Genodermatosis and Epidermolysis Bullosa (CEDIGEA), School of Medicine, University of Buenos Aires, Av. Córdoba 2351
Type of EB	EBS
Patient involvement	145 EBS patients giving small blood samples for genetic analysis
Funding amount	£15,000
Project length	1 year
Start date	November 2023
DEBRA internal ID	GR000045

 

Latest progress summary (2024):

Researchers have recruited 180 people with EB so far, either EB simplex or where the type wasn’t known. They have provided a genetic diagnosis for 104 of these people and, in doing so, identified 31 different genetic changes that cause EB, 12 of which have never been reported before. 

 

About our researchers:

Lead researcher: Dr Laura Valinotto is a researcher at Argentina’s National Scientific and Technical Research Council and a principal investigator (PI) at CEDIGEA. She holds an MSc in Biotechnology from the School of Biochemistry and Pharmacy at the National University of Rosario, Argentina and obtained her PhD degree at the School of Biochemistry and Pharmacy at the University of Buenos Aires, with her work on molecular epidemiology of respiratory paediatric viral infections at the Virology Lab in the Children’s Hospital R. Gutiérrez. While completing her PhD, she started to volunteer with the Dermatology Department of the hospital in order to find a way to diagnose genodermatosis patients attending the children’s public hospital. After some years, she was one of the founders of the Centre for Research in Genodermatosis and Epidermolysis Bullosa (CEDIGEA), at the University of Buenos Aires (UBA). Here she continues her work on molecular diagnosis of genodermatoses, together with epidemiological molecular research of the population in order to develop algorithms to perform cost-effective diagnosis of low-income patients and build detailed clinical and molecular records of EB to better understand the pathogenesis of the disease.

Co-researchers:

Prof Graciela Manzur is Professor and Head of the Department of Dermatology at the School of Medicine, University of Buenos Aires. She is a neonatologist, paediatrician and dermatologist and worked as a paediatric dermatologist at the R. Gutierrez Children’s Hospital for more than 15 years where she managed to open a new section of Rare Skin Diseases at the Hospital. After some years, and together with a multidisciplinary group, she founded the CEDIGEA, where she is the Director. After seeing so many children with EB grow up, she realised the necessity of a place where adult EB patients could be treated and she launched a second CEDIGEA centre, for adults, at the Hospital de Clínicas at the University of Buenos Aires.

Dr Mónica Natale is a biochemist involved in the molecular diagnosis of genodermatoses at the R Gutiérrez Children’s Hospital. She was also one of the founders of the CEDIGEA and is in charge of the molecular lab, identifying new EB cases and developing new strategies for the diagnosis of other genodermatoses.

 

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Why this research is important:

The individual benefit for each of our EB patients is that molecular diagnosis will be available for them to determine the type and subtype of EB and provide an unequivocal diagnosis which is essential to give the best care and genetic counselling. The collective benefit is that the collected information about variants prevalence may be useful in shortening the diagnostic odyssey for future patients... and offer a more accurate prognosis. Additionally, in populations with unexplored genetic background, these studies could reveal a previously unknown diversity of pathogenic variants that should be considered when defining targets for gene therapies.

Dr Valinotto

 

Researcher’s abstract:

Grant title: Molecular epidemiology of Epidermolysis Bullosa Simplex in Argentina.

One of the main objectives of the Centre for Research in Genodermatoses and Epidermolysis Bullosa (CEDIGEA) in Argentina is to provide all EB patients with an accurate diagnosis in order to better and more effectively address the symptoms they suffer from, manage pain, and provide the interdisciplinary care they need, regardless of their social condition. Our goal in this project is to characterize our patients clinically and molecularly since there are not many reports from EB in South America. At CEDIGEA, we have had the opportunity to publish a similar study with DEB and Kindler patients, and our goal is to complete and publish the study of EBS patients.

Our Centre for Research in Genodermatoses and Epidermolysis Bullosa (CEDIGEA) at the University of Buenos Aires diagnoses and follows up patients without health insurance in Argentina. The aim of this project is to discover the prevalence and diversity of genetic variants associated to EBS in our population, which has an unexplored background. Being able to report if novel variants are found in our region and building a database determine if new phenotypegenotype associations can be inferred is of utmost importance. This research project will, at the same time, allow us to offer our low-income patients a definitive molecular diagnosis free of charge.

With the help of the Buenos Aires Faculty and the efforts of CEDIGEA professionals, we had the opportunity to successfully carry out a previous project involving patients with DEB, where we diagnosed 181 patients from 136 unrelated families, finding 36 novel variants and a new phenotype-genotype association.

 

Researcher’s progress update (2024):

We've made significant progress in our project at the Centre for Research in Genodermatosis and Epidermolysis Bullosa (CEDIGEA). Currently, we've recruited 180 patients from 121 families who were referred to us due to clinical suspicion of Epidermolysis Bullosa Simplex (EBS) or other Epidermolysis Bullosa of undefined type.

Our main goal was to perform genetic analysis to provide molecular diagnoses, and at the same time to learn about the genetic basis of the disease in our population. So far, we've analysed specific genes and achieved a molecular diagnosis for 104 patients, which is a substantial accomplishment. In doing so, we've identified 31 different pathogenic variants, with 12 of them being previously unreported in the literature. 

However, challenges arose during our project. We encountered delays in acquiring necessary reagents for genetic sequencing due to economic instability and changing regulations in our country, with the prices of the laboratory supplies being 300% higher than three years ago. Due to these challenges, we've had to revise our strategy to make the most of our grant funds and ensure timely completion of our objectives. 

Regarding publications, we're preparing a comprehensive manuscript to present our findings. We believe that by studying such a large number of cases, we will be able to detect particularities in each patient and groups of patients, and this data will be useful to predict how the disease will develop in future patients. 

As for patient involvement, Magdalena and Josefina have been instrumental. Through their blog "En mi piel", they've provided valuable insights and created a platform for patients to share their experiences. This patient-centred approach guides our research focus and ensures that our work addresses the needs of those affected by Epidermolysis Bullosa and other rare skin diseases. 

In summary, despite the challenges, our project is progressing well, and we're committed to advancing research in the field of Epidermolysis Bullosa for the benefit of patients worldwide. 

And we don't want to miss this opportunity to invite you to the V Argentine Congress of Genodermatoses and Epidermolysis Bullosa, in virtual format, on September 19th, 20th, and 21st, 2024. To stay updated, follow us on our Instagram @cedigea.uba

(From May 2024 progress report.)

 

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