Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa

Conditions
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Junctional Epidermolysis Bullosa, Laryngo Onycho Cutaneous Syndrome

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Retrospective data regarding genetic information will be collected from participants' medical records. Deep phenotyping of participants will also be completed. | Other: No intervention<br>* No interventions present in this study.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open access database, Junctional Epidermolysis Bullosa, Genotype phenotype correlation