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Primary immunodeficiency

Gene: PSENEN

Amber List (moderate evidence)

PSENEN (presenilin enhancer gamma-secretase subunit)
EnsemblGeneIds (GRCh38): ENSG00000205155
EnsemblGeneIds (GRCh37): ENSG00000205155
OMIM: 607632, Gene2Phenotype
PSENEN is in 5 panels

3 reviews

Louise Daugherty (Genomics England Curator)

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.

Eleanor Williams (Genomics England Curator)

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.

Sophie Hambleton (Newcastle University)

I don't know

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

Phenotypes
hidradenitis suppurativa; acne inversa withor without Dowling-Degos disease

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • IUIS Classification December 2019
  • Expert Review Amber
  • IUIS Classification February 2018
Phenotypes
  • Defects in intrinsic and innate immunity
  • Acne inversa, familial, 2, with or without Dowling-Degos disease 613736
  • Defects in Intrinsic and Innate Immunity
  • Hidradenitis suppurativa
OMIM
607632
Clinvar variants
Variants in PSENEN
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Feb 2020, Gel status: 2

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

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

12 Jul 2018, Gel status: 2

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

6 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: psenen has been classified as Amber List (Moderate Evidence).

5 Jul 2018, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: PSENEN was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

5 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: psenen has been classified as Amber List (Moderate Evidence).

5 Jul 2018, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

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

5 Jul 2018, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PSENEN were set to 20929727; 21412258; 27900998; 28287404; 28601418; 23439959; 23020871; 28922471

1 Jul 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene PSENEN were set to Hidradenitis suppurativa, Defects in Intrinsic and Innate Immunity

26 Jun 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

PSENEN was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018

26 Jun 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

PSENEN was created by Louise Daugherty