COVID-19 researchGene: PSENEN
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): PSENEN .PanelApp HGNC gene symbol check: PSENEN . IUIS Disease: PSENEN deficiency hidradenitis suppurativa . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: Epidermis. IUIS Associated features: Hidradenitis suppurativa. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Other Inborn Errors of Immunity Related to Non-Hematopoietic Tissues
Created: 6 Jul 2018, 3:48 p.m.
Comment on list classification: Rating as Amber on advice of Genomics England clinical team.
Created: 5 Jul 2018, 9:12 p.m.
Comment on phenotypes: Added phenotype from OMIM
Created: 5 Jul 2018, 3:29 p.m.
Comment on publications: Added publications relevant to the association with the phenotype, and the nature of the phenotype.
Created: 5 Jul 2018, 3:28 p.m.
Consulting with Genomics England clinical team on the rating for this gene.
Created: 5 Jul 2018, 3:16 p.m.
In OMIM PSENEN is associated with Acne inversa, familial, 2, with or without Dowling-Degos disease. Several studies report patients with this disorder and variants in the PSENEN gene (Wang et al. (2010) (PMID: 20929727]), Pink et al. (2011)(PMID: 21412258), Zhou et al. (2016) (PMID: 27900998), Ralser et al. (2017) (PMID: 28287404), Li et al. (2017) (PMID: 28601418)) - 13 families in total, 7 different variants reported in OMIM. OMIM reports that Li et al. (2017) observed intrafamilial variability in severity of lesions, which they suggested might be due to reduced penetrance involving different genetic and environmental factors. Wollina et al. (2013)(PMID: 23439959) review the pathogenesis and treatment of Acne inversa (Hidradenitis suppurativa) and describe the possible role of the immune system in this disorder. PSENEN is part of the gamma-Secretase complex which is involved in the regulation of the canonical Notch signalling pathway. Melnik and Plewig (2013)(PMID: 23020871) describe a model for impaired Notch signalling affecting the immune functions of T helper cells (Figure 2). However, impairment of Notch signalling may also contribute to other clinical manifestations of the disorder such as inhibition of the hair growth cycle, conversion of hair follicles intocysts, and inhibition of sebaceous gland differentiation (Pavlovsky et al. (2017)(PMID: 28922471).
Created: 5 Jul 2018, 3:10 p.m.
Classified by IUIS as a defect of intrinsic or innate immunity
Created: 30 Jun 2018, 5:51 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
hidradenitis suppurativa; acne inversa withor without Dowling-Degos disease
Source Expert Review Green was added to PSENEN. Added phenotypes Acne inversa, familial, 2, with or without Dowling-Degos disease 613736; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity; Hidradenitis suppurativa for gene: PSENEN Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: PSENEN was added gene: PSENEN was added to Viral susceptibility. Sources: IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber Mode of inheritance for gene: PSENEN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PSENEN were set to 23439959; 28601418; 28287404; 23020871; 20929727; 32086639; 21412258; 27900998; 32048120; 28922471 Phenotypes for gene: PSENEN were set to Acne inversa, familial, 2, with or without Dowling-Degos disease 613736; Defects in intrinsic and innate immunity; Defects in Intrinsic and Innate Immunity; Hidradenitis suppurativa