Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa

Junctional Epidermolysis Bullosa Clinical Trial

Official title:

Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04727268
• Other study ID #: RRK7326
• Status: Enrolling by invitation
• Start date: September 27, 2021
• Est. completion date: December 30, 2021

Study information

• Verified date: September 2021
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This study will collect genetic and clinical information of junctional epidermolysis bullosa (JEB) patients. Computer analysis will be performed on genetic mutations found in these patients and this will be correlated with their clinical characteristics.

Description:

Junctional epidermolysis bullosa (JEB) is a rare genetic skin disease where genetic defects in skin proteins result in extensive blistering in response to mild mechanical stress. Patients are often affected at birth or from early childhood, and suffer from varying degrees of severity depending on the specific mutations that they have and the proteins that are affected. This ranges from severe widespread blistering and death within the first few years of life, to minimal localised blistering and survival to adulthood. Diagnosis is confirmed by genetic testing, and this is often used to predict the likely clinical course. However, it is not always straightforward to make accurate predictions from genetic information, as our understanding of these proteins and mutations at the molecular level is currently incomplete.

The main aim of this project is to systematically collect genetic and clinical data of junctional epidermolysis bullosa (JEB) patients and to explore whether there are any relationships between participants' genetic defects and the severity of disease. This will help in establishing links between genetic defects and clinical characteristics, which is essential for accurate prognostication, genetic counselling and prenatal diagnosis.

This study will also aim to develop pipelines for analysis of how mutations may affect corresponding protein structure and function using computer prediction tools. This will improve our understanding of how these proteins function, and could partly explain the variation in disease severity of patients with this condition. It could also lead to identification of important regions of the protein, which could be investigated further in subsequent studies.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

Inclusion Criteria:

Adults and children with a diagnosis of JEB or LOC syndrome, which has been confirmed with genetic testing. A mutation is present in one of the following genes: LAMA3, LAMB3, LAMC2 or COL17A1.

Current JEB patients, or JEB patients within the last 5 years who have used the EB service at Solihull hospital or Birmingham Women's and Children's Hospital. This includes patients who are living and also those who passed away in the last 5 years (eg from severe JEB).

Exclusion Criteria:

Adult patients who are unable to give informed consent. Child patients who do not assent and/ or have no one appropriate who can consent on their behalf.

Persons who might not adequately understand verbal explanations or written information given in English.

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Epidermolysis Bullosa, Junctional
• Junctional Epidermolysis Bullosa
• Laryngo Onycho Cutaneous Syndrome

Intervention

Other:
• No intervention
No interventions present in this study.

Locations

Country	Name	City	State
United Kingdom	Solihull Hospital	Solihull	West Midlands

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust	Dystrophic Epidermolysis Bullosa Research Association (DEBRA), University of Birmingham

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Bardhan A, Bruckner-Tuderman L, Chapple ILC, Fine JD, Harper N, Has C, Magin TM, Marinkovich MP, Marshall JF, McGrath JA, Mellerio JE, Polson R, Heagerty AH. Epidermolysis bullosa. Nat Rev Dis Primers. 2020 Sep 24;6(1):78. doi: 10.1038/s41572-020-0210-0. Review. — View Citation

Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L, Diem A, Fine JD, Heagerty A, Hovnanian A, Marinkovich MP, Martinez AE, McGrath JA, Moss C, Murrell DF, Palisson F, Schwieger-Briel A, Sprecher E, Tamai K, Uitto J, Woodley DT, Zambruno G, Mellerio JE. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020 Oct;183(4):614-627. doi: 10.1111/bjd.18921. Epub 2020 Mar 11. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genotype and phenotype data collection	The primary objective is to systematically collect genetic and clinical data of junctional epidermolysis bullosa (JEB) patients and to explore whether there are any relationships between participants' genetic defects and the severity of disease.	6 months
Secondary	Bioinformatic analysis	Development of a pipeline for bioinformatic analysis of variants	10 months