Janire Perurena-Prieto, Spain
Hospital U. Vall d'Hebron ImmunologyPresenter of 1 Presentation
IDENTIFICATION OF A DOMINANT ACTIVATING RAC2 MUTATION IN A PATIENT WITH ATYPICAL EPIDERMODYSPLASIA VERRUCIFORMIS
Abstract
Background and Aims
Epidermodysplasia verruciformis (EV) is characterized by susceptibility to human β-papillomavirus (β-HPV) infection and is strongly associated with skin carcinomas. Typical EV is caused by mutations in two proteins involved in the keratinocyte-intrinsic immunity, EVER1 and EVER2. However, clinical symptoms of EV have been associated with a variety of mutations causative of T cell defects. The aim of this study was to identify a possible primary immunodeficiency in a patient with a severe atypical EV.
Methods
A 32-year-old woman presented with multiple overinfected ulcers. She was diagnosed of EV during her infancy due to her skin lesions. She has been suffering from multiple squamous-cell carcinomas since she was 20. A stable circulating monoclonal CD4+/CD8+ T-cell population was demonstrated accounting 10% of total lymphocytes. A hypocellular bone marrow was detected on a biopsy. A high-risk HPV was found on a cervical cytology. Lymphocyte subpopulations were analyzed by an extensive flow cytometry study. A targeted NGS panel focused in genes causing primary immunodeficiencies was performed to achieve the genetic diagnosis.
Results
General lymphopenia was detected, with severely diminished B cells. IgG levels were slightly low. CD4+ T cells showed an effector-memory phenotype, mainly Th1-T17. CD8+ T cell showed a terminally differentiated (CCR7lowCD45RAhigh) phenotype. A recently described dominant activating mutation (c.101C>A/p.P34H) was found in RAC2 gene coding the small GTPase, RAC2.
Conclusions
This is the first reported case with activating RAC2 mutation presenting as an atypical EV. Additional in vitro studies are being conducted for a better functional characterization of this mutation.