Genetic bases of familial Systemic sclerosis
(2026)
Files
Thesis_Pierre_Maus_2026_Format_Livret.pdf
Embargo Access until 2030-03-12 - Adobe PDF
- 10.13 MB
Details
- Authors
- Supervisors
; Smith, Vanessa- Abstract
- Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular defects, immune dysregulation, and fibrosis. My project aimed to identify and functionally test genes that may contribute to disease pathogenesis. To this end, whole exome sequencing was performed on DNA from six families, each including two affected relatives. Variants were filtered to retain those shared within each family, rare in the general population, and predicted to affect protein function. Functional annotation highlighted genes regulating the cGAS-STING axis across all families, suggesting a potential role for this innate immune pathway in SSc. PRKD2, with variants of interest identified in two families, was prioritized for in vitro study. Using knock-in JURKAT cells, we showed that both PRKD2 variants alter protein activation and localization, and enhance T cell activation and signaling, supporting a role for this gene in immune dysregulation in SSc.
- Affiliations
Citations
Maus, P. (2026). Genetic bases of familial Systemic sclerosis. https://hdl.handle.net/2078.5/275644