Autoinflammatory & rare systemic diseases
De Novo Gain‐Of‐Function Variations in LYN Associated With an Early‐Onset Systemic Autoinflammatory Disorder
Authors' conclusion
This study demonstrates the pathogenicity of the first 3 LYN variations identified in SAID patients and delineates the phenotypic spectrum of a disease entity characterized by severe, early-onset, systemic inflammatory disease affecting neonates with no family history of SAID. All 3 LYN variations affect the same tyrosine residue located in the C-terminus of Lyn, thereby demonstrating the critical role of this residue in the proper regulation of Lyn activity in humans.
Study context
- Population
- A patient presenting since birth with a severe systemic autoinflammatory disorder (SAID): recurrent fever, chronic urticaria, atopic dermatitis, arthralgia, increased inflammatory biomarkers and elevated plasma cytokines
- Outcome
- Functional consequences of LYN variations p.Tyr508His, p.Tyr508Phe and p.Tyr508*
Methodological detailstargeted next-generation sequencing, in vitro functional studies
- Targeted next-generation sequencing
- In vitro functional studies
Main finding
As reported in the abstract
- De novo LYN variation (p.Tyr508His) identified in the patient
- All 3 variations prevent phosphorylation of residue 508 and lead to autophosphorylation of Tyr397
- All 3 LYN variations activate the NF-κB pathway
- Gain-of-function effect of the Tyr508 variations on Lyn activity
Original publication
De Novo Gain‐Of‐Function Variations in LYN Associated With an Early‐Onset Systemic Autoinflammatory Disorder. Arthritis Rheumatol. Published 28 December 2022. doi:10.
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