Academic research community (GECIP)

Hereditary palmoplantar keratodermas (hPPKs) are a group of different skin conditions that arise due to gene variants. They are grouped together as they all cause a similar thickening of the palms and soles similar to calluses. This can cause symptoms such as pain and itch, as well as issues arising from the physical appearance. Not all hPPKs have a known cause, and so we will investigate data from 90 participants with these conditions to look for new genetic causes. The aim of this research is to be able to give patients a more accurate diagnosis in clinic the future as new treatments are likely to be based on genetic diagnosis.

Eczema is common and is associated with an increased risk of asthma and hay fever. Eczema, asthma, and/or hayfever are all “atopic” diseases, and affected patients often have a family member with at least one of these diseases. We know genes play a role but our understanding is still quite poor. In this project we will look for new genes that may be involved in eczema, asthma, and hayfever using genetic data from 89 individuals who took part in The 100,000 Genomes Project. We think this is important as identifying new genes may help develop new treatments.

Changes in the gene, TSPEAR, have been reported to cause a particular disorder which affects the development of skin, hair, teeth and sweat glands. Conditions like this a called ectodermal dysplasias and there are many other causes. Only a handful of patients with variants in TSPEAR have been described so it is difficult to truly understand the full spectrum of problems that can occur with this disorder. We would like to use the 100, 000 Genomes Project data to find and describe more patients with this condition.

This research project is approved, but is not approved for publication. Epidermolysis Bullosa or EB is a rare genetic disease that is characterized by severe blistering of skin, chronic wounds and damage. Severe forms of the disease can result in injuries to internal organs leading to progressive damage and eventually death at very young age. Diagnosis of the disease is primarily based on gene sequencing at previous established hot-spots. There are routine gene-based diagnostic tests available for detection of the most common genes known to cause EB. However, diagnosis is complicated, such as the incidence of wounds for potential unidentified gene(s), presence of similar phenotypic and clinical presentations of EB with very different underlying causative gene/mutation, and presence of wide spectrum heterogeneity of clinical phenotype adding complexity to establish direct genetic defect to viable and adequate therapeutic strategy. Given the significant advances of gene sequencing in parallel to multi-omic technology (proteomic, lipidomic and metabolomic capture) and artificial-intelligence analytics there is now potential to establish the phenotypic basis underlying gene aberration in disease causation.

Generalised pustular psoriasis (GPP) is a rare and severe disorder, manifesting with the appearance of painful pustules on inflamed skin. Disease episodes are also accompanied by high fever and sharp increases in white-blood cell counts (leucocytosis). As a result, patients experiencing GPP flares require immediate hospitalization. While 20% of GPP sufferers carry variants in a gene called IL36RN, the cause of the disease remains unknown for the majority of cases. Thus, the aim of this project is to identify additional genes that are mutated in GPP patients, with a view to improving our understanding of the disease and facilitating its genetic diagnosis. Of note, the combination of skin rashes, recurrent fevers and leucocytosis is also observed in other inflammatory conditions. Thus, we will seek to determine whether any newly identified GPP gene is also mutated in other diseases presenting with similar clinical features.