SERPINA12 Splice Site Variant in Tunisian Familial Psoriasis Vulgaris: Segregation to Inheritance
- 1Laboratory of Molecular and Functional Genetics, Faculty of Sciences of Sfax, Sfax University, Sfax 3029, Tunisia
Abstract
BackgroundPsoriasis 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.
ObjectiveTo identify genetic variants associated with PV and elucidate their impact on disease pathogenesis and metabolic comorbidities.
MethodsWhole 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.
ResultsWe 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 vaspins anti-inflammatory activity via kallikrein 7 (KLK7) inhibition.
ConclusionThis 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.
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BibTeX
@misc{ennouri2026serpina12,
title = {{SERPINA12 Splice Site Variant in Tunisian Familial Psoriasis Vulgaris: Segregation to Inheritance}},
author = {M. Ennouri and S. Marrakchi and F. Frikha and E. B. Bahloul and A. B. H. Ltaief and R. Ammar and H. Turki and N. B. Elleuch},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.26362406},
url = {https://www.medrxiv.org/content/10.64898/2026.09.11.26362406v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - SERPINA12 Splice Site Variant in Tunisian Familial Psoriasis Vulgaris: Segregation to Inheritance
AU - M. Ennouri
AU - S. Marrakchi
AU - F. Frikha
AU - E. B. Bahloul
AU - A. B. H. Ltaief
AU - R. Ammar
AU - H. Turki
AU - N. B. Elleuch
PY - 2026
DA - 2026/09/11
PB - medRxiv
DO - 10.64898/2026.09.11.26362406
UR - https://www.medrxiv.org/content/10.64898/2026.09.11.26362406v1
AB - BackgroundPsoriasis 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. ObjectiveTo identify genetic variants associated with PV and elucidate their impact on disease pathogenesis and metabolic comorbidities. MethodsWhole 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. ResultsWe 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 vaspins anti-inflammatory activity via kallikrein 7 (KLK7) inhibition. ConclusionThis 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.
ER -