The Project

This Project was funded by FONDECYT Chile (#11140440), and was entitled “Determining the genetic basis of epidermolysis bullosa symptoms through genotype-phenotype associations using next generation sequencing”. It is a 3-year project that started on November 2014.

Epidermolysis bullosa (EB) is a name given to a group of monogenic diseases characterized by skin blistering due to genetically defective or absent basal membrane zone components. Patients suffering from this disease have excessive skin and mucosal fragility producing painful blisters with minor trauma. It is estimated that around half a million people suffer from EB worldwide, with an incidence of 1 in 50,000 newborns.

EB is characterized by heterogeneous clinical symptoms and genetic etiology. To date, there are 19 described disease-causing genes and a large variety of clinical manifestations of the disease, ranging from mild to life-threatening, which makes it a very difficult disease to diagnose and to estimate patient prognosis.

In 2014, and with the motivation to improve patient diagnosis and prognosis, we initiated a three year project, which is presented here. Our hypothesis was that most – if not all – EB phenotypes have a genetic basis and a genotype-phenotype association study would help to decipher them.

The project consisted of collecting Genotypic (mutations) and Phenotypic (clinical signs and symptoms) data from Chilean EB patients, over the course of two years. Patients from all EB types were eligible for enrollment. Mutational data was compiled by taking a sample of peripheral blood or saliva, extracting the genomic DNA and analyzing it by a next generation sequencing (NGS) custom-made EB panel. Phenotypic data of each patient was collected using questionnaires, one for each clinical area: dermatology, pediatrics, ophthalmology, odontology and otorhinolaryngology. Clinical evaluations were carried out for a period of 2 years and patients could only be evaluated in 1 or all 5 of the clinical areas.

This project has been reviewed and approved by the pertinent ethics committees: Facultad de Medicina Universidad del Desarrollo (UDD), Servicio de Salúd Metropolitano Sur Oriente (SSMSO) and Facultad de Odontología Universidad de Chile.

Collected data is currently presented and shared with the EB community through this database.

The Team

This study was a joint effort from several national and international institutions, all with the same goal, to “increase the understanding of EB disease and to help patients”. All these professionals were involved at different stages of the project, either during the project elaboration, project development and/or data processing. See the institutions and the people involved below.


  1. DEBRA Chile

  2. Centro de Genética y Genómica, Facultad de Medicina, UDD, Chile
  3. Hospital Padre Hurtado, Chile
  4. Clínica Alemana de Santiago (CAS), Chile
  5. Facultad de Odontología, Universidad de Chile
  6. Fundación Oftalmológica Los Andes (FOLA), Chile
  7. EB Haus, Salzburg, Austria


  • Ignacia Fuentes, PhD: Project Leader (1,2). Dr. Fuentes incorporated the Medical Technologist, Sofia Burattini, and the Registered Nurse, Pilar Morandé, in this research.

  • María Joao Yubero, MD: Clinical evaluations (1,3,4)

  • Francis Palisson, MD: Clinical evaluations (1,3,4)

  • Maria Elena McNab, MD: Clinical evaluations (1)

  • Constanza Fuentes, MD: Clinical evaluations (1)

  • José Miguel Contreras, MD: Clinical evaluations (4) . Dr. Contreras incorporated a clinical resident in this research: Dr. Pilar Contreras.

  • Susanne Kramer, DDS: Clinical evaluations (5) . Dr. Kramer incorporated two undergraduate students in this project: Carolina Encina and José Farfán.

  • Arturo Kantor, MD: Clinical evaluations (6) . Dr. Kantor incorporated a clinical resident in this research: Dr. Felipe Mellado.

  • Johann Bauer, MD: Mutational data collection (7) . Dr. Bauer incorporated his research team in the project, especially Alfred Klausseger.

Pilar Morande, Sofía Burattini and Dr. Ignacia Fuentes.
Dr. Ignacia Fuentes presenting at the EB Patient & Research meeting in Santiago, July 2017.
Dr. Johann Bauer and Alfred Klausseger in Salzburg, Austria 2014.
Dr. Ignacia Fuentes presenting the results of the FONDECYT Project at the SID Meeting 2017 in Portland, USA.
Dr. Ignacia Fuentes, Francis Palisson, Arturo Kantor and others presenting at the EB Symposium during the ICD 2017 in Buenos Aires, Argentina.
Dr. Susanne Kramer.


Genomic DNA was extracted from all patients enrolled in this study, either from peripheral blood or saliva samples. Mutations were analyzed by running the samples in a custom-made next generation sequencing(NGS) panel, carried out in collaboration with the EB Haus in Austria. The panel contained the 18 EB disease-causing genes (as described up to 2014) and other 12 genes related to other skin diseases (common differential diagnosis of EB). Samples were further analyzed with bioinformatic tools to decipher the pathogenic variant (dominant inheritance) or variants (recessive inheritance) that caused the disease in each patient.

A total of 186 samples were collected and sequenced. From those 186, we could confirm a molecular diagnosis in 154 patients (83% sensibility). In the remaining 32 patients, we found 1) only 1 recessive mutation, 2) variants with unknown significance that need further study or 3) no variants.

Pathogenic mutations in our patient cohort were harbored in 8 genes: KRT5, KRT14, EXPH5, TGM5, LAMB3, PLEC, COL7A1 and FERMT1. Sixty patients had a dominant inheritance and 102 had a recessive inheritance (the remaining patient/mutations are not confirmed).

Simplex EB KRT5 27
TGM5 18
KRT14 7
Junctional EB LAMB3 13
Dystrophic EB COL7A1 91
Kindler Syndrome FERMT1 1


All patients from whom we collected a biological sample for mutational analysis were eligible and encouraged to participate in this part of the project. The collection of phenotypic data consisted of evaluating patients for clinical signs and symptoms in up to 5 different clinical areas: Dermatology, Pediatrics, Ophthalmology, Odontology and Otorhinolaryngology. For the first 4 clinical areas, the evaluation was mainly observational and by filling in a questionnaire. However, because the otorhinolaryngology evaluation needs an invasive procedure, only patients with clinical signs of respiratory tract involvement were sent for evaluation.

Evaluations were carried out by the area-specific health care team. Each patient could be evaluated only once per clinical area and at any time during the first 2 years of the project. Thus, their overall evaluation age is X +/- 2 years old.

After completing the first 2 years of the project, the total number of clinical evaluations performed was:

  • 149 for Dermatology

  • 131 for Pediatrics

  • 72 for Odontology

  • 64 for Ophthalmology

  • 12 for Otorhinolaryngology

Dermatology Pediatrics Odontology Ophthalmology Otorhinolaryngology