Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: PSENENOriginaI 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 TissuesCreated: 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 OMIMCreated: 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 immunityCreated: 30 Jun 2018, 5:51 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
hidradenitis suppurativa; acne inversa withor without Dowling-Degos disease
Publications
Source IUIS Classification December 2019 was added to PSENEN. Added phenotypes Defects in intrinsic and innate immunity; Hidradenitis suppurativa for gene: PSENEN Publications for gene PSENEN were updated from 20929727; 21412258; 27900998; 28287404; 28601418; 23439959; 23020871; 28922471 to 21412258; 28601418; 23439959; 32048120; 27900998; 28287404; 20929727; 28922471; 23020871; 32086639
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: psenen has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: PSENEN was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: psenen has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: PSENEN were set to Hidradenitis suppurativa; Defects in Intrinsic and Innate Immunity; Acne inversa, familial, 2, with or without Dowling-Degos disease 613736
Publications for gene: PSENEN were set to 20929727; 21412258; 27900998; 28287404; 28601418; 23439959; 23020871; 28922471
Phenotypes for gene PSENEN were set to Hidradenitis suppurativa, Defects in Intrinsic and Innate Immunity
PSENEN was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018
PSENEN was created by Louise Daugherty