Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Junctional Epidermolysis Bullosa; Laryngo Onycho Cutaneous Syndrome
• Intervention / Treatment: Other: No intervention

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Solihull, West Midlands, United Kingdom, B91 2JL
      • Solihull Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with JEB, confirmed through genetic testing.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Retrospective data regarding genetic information will be collected from participants' medical records. Deep phenotyping of participants will also be completed.	Other: No intervention; No interventions present in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioinformatic analysis	Development of a pipeline for bioinformatic analysis of variants	10 months

Collaborators and Investigators

• Sponsor: University Hospital Birmingham NHS Foundation Trust
• Collaborators: University of Birmingham; Dystrophic Epidermolysis Bullosa Research Association (DEBRA)

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2021
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: January 22, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Open access database; Junctional Epidermolysis Bullosa; Genotype phenotype correlation
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases, Vesiculobullous; Skin Abnormalities; Epidermolysis Bullosa; Epidermolysis Bullosa, Junctional
• Other Study ID Numbers: RRK7326

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Once data collection and analysis has been completed, anonymised data regarding genotype and phenotype will be presented at scientific meetings and publised in journals and / or postgraduates theses.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No