Vasculitis

Gene: LYN

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autoinflammatory disease, systemic, with vasculitis, MIM# 620376

Green List (high evidence)

Three unrelated individuals from described with three distinct de novo variants in LYN, p.Y508*, p.Q507* and a missense variant, p.Y508F. The PTC variants do not cause NMD, and all three variants have been shown to result in constitutively active LYN kinase by preventing inhibitory phosphorylation of the Y508 regulatory tyrosine. Extensive functional data to confirm gain-of-function effect was presented.

Patient presented perinatally with immunological symptoms, including diffuse purpuric skin lesions, fever, and increased C-reactive protein (CRP). mild anemia, mild leukocytosis, moderate to severe thrombocytopenia. The patients with PTC were more severe, developing liver fibrosis and signs of cirrhosis.

All three patients responded to various degrees to treatment with src kinase inhibitors, dasatinib, etanercept and/or colchicine. Authors named the condition Lyn kinase-associated vasculopathy and liver fibrosis (LAVLI).

A fourth patient with a Tyr508His has also been described and presented with since birth with recurrent fever, chronic urticaria, atopic dermatitis, arthralgia, increased inflammatory biomarkers, and elevated plasma cytokine levels. Other features not consistent with LYN disease were attributed to prematurity (following maternal HELLP syndrome) and potentially other genetic factors.

Created: 6 Apr 2023, 3:03 a.m. | Last Modified: 6 Apr 2023, 3:27 a.m.

Panel Version: 0.74

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Vasculitis, MONDO:0018882, LYN-related

Publications

• 36932076
• 36122175

Mode of pathogenicity
Other

Red List (low evidence)

Comment when marking as ready: No human disease association published. Mouse models suggest role in autoinflammatory pathways.

Created: 9 May 2022, 5:19 a.m. | Last Modified: 9 May 2022, 5:19 a.m.

Panel Version: 0.64

Mice homozygous for a disruption of the Lyn locus display abnormalities associated with the B-lymphocyte lineage and in mast cell function. No human disease association published.

Created: 9 May 2022, 5:08 a.m. | Last Modified: 9 May 2022, 5:08 a.m.

Panel Version: 0.62

Mode of inheritance
Unknown