Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: LYN
Comment on list classification: There is sufficient evidence available (four unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.Created: 2 Jan 2024, 2:40 p.m. | Last Modified: 2 Jan 2024, 2:40 p.m.
Panel Version: 4.130
As reviewed by Boaz Palterer, there are four unrelated patients reported with systemic autoinflammatory disorder (SAID) and identified with de novo LYN variants. Of these one patient was reported in PMID:36122175 and three unrelated boys were reported in PMID:36932076. The patient data was also supported by functional evidence, which suggested gain of function mechanism for LYN variants.
This gene was associated with relevant phenotypes in OMIM (MIM #620376), but not yet in Gene2Phenotype.Created: 2 Jan 2024, 2:37 p.m. | Last Modified: 2 Jan 2024, 2:37 p.m.
Panel Version: 4.125
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autoinflammatory disease, systemic, with vasculitis, OMIM:620376
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Louvrier et al. described 1 patient ( PMID 36122175 ) and De Jesus et al ( https://www.medrxiv.org/content/10.1101/2022.09.27.22280319v1.full.pdf ) 3 additional patients, for a total of 4 kindreds with de novo LYN mutations.
Strong functional evidence: p.Tyr508His, p.Tyr508Phe and p.Tyr508* cause inhibition loss, leading to Tyr397 autophosphorylation and functional GOF.
Sources: LiteratureCreated: 3 Oct 2022, 4 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Autoinflammatory; Neutrophilic vasculitis; Liver fibrosis; Chronic urticaria; Atopic dermatitis; Fever
Publications
Gene: lyn has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: LYN were changed from Autoinflammatory; Neutrophilic vasculitis; Liver fibrosis; Chronic urticaria; Atopic dermatitis; Fever to Autoinflammatory disease, systemic, with vasculitis, OMIM:620376
Publications for gene: LYN were set to 36122175
Mode of pathogenicity for gene: LYN was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for gene: LYN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q4_23_promote_green tag was added to gene: LYN.
gene: LYN was added gene: LYN was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: LYN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: LYN were set to 36122175 Phenotypes for gene: LYN were set to Autoinflammatory; Neutrophilic vasculitis; Liver fibrosis; Chronic urticaria; Atopic dermatitis; Fever Penetrance for gene: LYN were set to unknown Review for gene: LYN was set to GREEN