SERPINA12 Splice Site Variant in Tunisian Familial Psoriasis Vulgaris: Segregation to Inheritance
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Background
Psoriasis vulgaris (PV) is an inflammatory skin disorder whose genetic basis has been widely explored through genome-wide association studies and biomarker analyses in heterogeneous cohorts. We adopted a family-based strategy focusing on nuclear families.
Objective
To identify genetic variants associated with PV and elucidate their impact on disease pathogenesis and metabolic comorbidities.
Methods
Whole exome sequencing (WES) was performed on a PV affected nuclear families. Integrative computational analyses, including structural modeling and molecular dynamics simulations, were used to evaluate the impact of identified variants on protein stability and function. Potential links to inflammation and metabolic dysfunction were explored through literature-based interpretation.
Results
We identified a heterozygous splice site variant c.905+1 G>T in the SERPINA12 gene that segregates with PV in the studied families. Structural modeling and molecular dynamics revealed destabilization of the C-terminal region, impairing its serine protease inhibitory function. This alteration reduces vaspin’s anti-inflammatory activity via kallikrein 7 (KLK7) inhibition.
Conclusion
This integrative WES-based approach identifies a PV associated mutation and suggests a new pathogenic mechanism involving the vaspin/KLK7 axis. As these molecules are expressed in the skin and may influence insulin activity, these findings offer insight into the link between PV and type 2 diabetes mellitus and highlight potential targets for precision medicine in psoriasis and associated metabolic disorders.
