Clinical trial NCT04727268: Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa
Official title: Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Junctional Epidermolysis Bullosa
Laryngo Onycho Cutaneous Syndrome
Keywords: Open access database
Junctional Epidermolysis Bullosa
Genotype phenotype correlation
Lead sponsor: University Hospital Birmingham NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Dystrophic Epidermolysis Bullosa Research Association (DEBRA)
name: University of Birmingham
First posted: 2021-01-27
Enrollment: 20
Sex: ALL
Minimum age (years): 0
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with JEB, confirmed through genetic testing.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Genotype and phenotype data collection
timeFrame: 6 months
Secondary outcomes:
measure: Bioinformatic analysis
timeFrame: 10 months
Other outcomes:
Locations:
city: Solihull
country: United Kingdom
facility: Solihull Hospital
state: West Midlands
Study officials:
References:
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.
citation: 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.