Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: NLRP1
Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants in this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.Created: 2 Nov 2023, 2:20 p.m. | Last Modified: 2 Nov 2023, 2:42 p.m.
Panel Version: 4.113
There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be gain-of-function.
This gene has been associated with multiple relevant phenotypes in both OMIM and Gene2Phenotype (eye panel).Created: 2 Nov 2023, 2:13 p.m. | Last Modified: 2 Nov 2023, 2:43 p.m.
Panel Version: 4.113
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Autoinflammation with arthritis and dyskeratosis, OMIM:617388; ?Respiratory papillomatosis, juvenile recurrent, congenital, OMIM:618803; Palmoplantar carcinoma, multiple self-healing, OMIM:615225; {Vitiligo-associated multiple autoimmune disease susceptibility 1}, OMIM:606579
Publications
Mode of pathogenicity
Other
PMID: 31873740 report another patient with disease due to this gene - het missense variant in a patient with inflammatory corneal intraepithelial dyskeratosis, mucosal inflammation, tooth abnormalities and, eczema. Positive family history suggested autosomal dominant inheritance with incomplete penetrance.Created: 18 Oct 2023, 11:51 a.m. | Last Modified: 18 Oct 2023, 11:51 a.m.
Panel Version: 4.50
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Autoinflammatory disease with corneal and mucosal dyskeratosis
Publications
Comment on list classification: Changed rating of gene from Red to Amber. This gene was rated as Amber in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 12:14 p.m. | Last Modified: 14 Oct 2020, 12:14 p.m.
Panel Version: 2.213
The following PubMed IDs were added to entity NLRP1: 27965258. These publications have been associated with OMIM phenotype MIM#617388, which is listed for this entity, by the autoinflammation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Publications
PMID:27662089: Zhong et al., 2016 report germline GOF variants in NLRP1 which cause two overlapping skin disorders (MSPC and FKLC), linking NLRP1 to skin inflammatory syndromes.Created: 29 Apr 2020, 8:33 p.m. | Last Modified: 29 Apr 2020, 8:33 p.m.
Panel Version: 2.138
PMID:31484767: Drutman et al., 2019 report 2 siblings with syndromic JRRP and a homozygous GOF variant in NLRP1.Created: 29 Apr 2020, 8:33 p.m. | Last Modified: 29 Apr 2020, 8:33 p.m.
Panel Version: 2.138
Multiple phenotypes resulting from abnormal inflammatory response associated with this gene, both mono-allelic and bi-allelic, some gain-of-function (including bi-allelic).
Bi-allelic disease: single family with dyskeratosis, autoimmunity and arthritis and another family with bi-allelic GoF and recurrent respiratory papillomatosis phenotype
Mono-allelic disease: mostly pertains to the association with multiple self-healing palmoplantar carcinomas (MSPC). One consanguineous family in which a sister and brother with clinical features of MSPC as well as multiple discrete and semiconfluent lichenoid papules on the arms, legs, and lower trunk were homozygous for an in-frame deletion in the NLRP1 gene, and parents had milder skin defects. The clinical diagnosis in this family was familial keratosis lichenoides chronica (Nekam disease).Created: 11 Apr 2020, 4:44 a.m. | Last Modified: 11 Apr 2020, 4:44 a.m.
Panel Version: 2.51
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Autoinflammation with arthritis and dyskeratosis, MIM# 617388; Palmoplantar carcinoma, multiple self-healing 615225; Recurrent respiratory papillomatosis
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Original Metadata from IUIS classification table (December, 2019). IUIS Genetic defect (original gene symbol in IUIS download): NLRP1 .PanelApp HGNC gene symbol check: NLRP1 . IUIS Disease: NLRP1 deficiency . IUIS Inheritance: AR / AD GOF .T cells: Normal / Normal, .B cells: Normal / Normal, Immunoglobulin levels: Normal / Normal, Neutrophil count: Normal / Normal IUIS Other affected cells: leukocytes / Keratinocytes. IUIS Associated features: Dyskeratosis, autoimmunity and arthritis / Palmoplantar carcinoma, corneal scarring, IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the InflammasomeCreated: 28 Feb 2020, 4:41 p.m. | Last Modified: 28 Feb 2020, 4:41 p.m.
Panel Version: 2.27
Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber.Created: 12 Nov 2019, 5:02 p.m. | Last Modified: 12 Nov 2019, 5:02 p.m.
Panel Version: 1.137
Autoinflammation - two cases, ?AD / AR – unclearCreated: 26 Sep 2019, 3:57 p.m. | Last Modified: 26 Sep 2019, 3:57 p.m.
Panel Version: 1.130
Comment on list classification: Upgraded from Red to Amber. This is a relevant phenotype but there is not enough evidence in the literature to date (only two reported cases) and there has been no further evidence in terms of unpublished cases other than a Green rating recommendation from the Immunology Specialist Test Group. To remain Amber unless further supporting evidence from the Test Group.Created: 17 Sep 2019, 5:14 p.m. | Last Modified: 17 Sep 2019, 5:22 p.m.
Panel Version: 1.101
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on publications: PMID: 29850521- Psoriasis Vulgaris RiskCreated: 6 Jul 2018, 3:36 p.m.
Comment on publications: added publications suggested from external expert reviewCreated: 6 Jul 2018, 3:13 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NLRP1 .PanelApp HGNC gene symbol check: NLRP1 . IUIS Disease: NLRP1 deficiency . IUIS Inheritance: AR .T cells: Normal, .B cells: N/A, .IUIS Other affected cells: leukocytes. IUIS Associated features: Dyskeratosis, autoimmunity and arthritis. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the InflammasomeCreated: 6 Jul 2018, 12:30 p.m.
Publications
Single report, 2 sibs with homozygous variant and one singleton with a heterozygous missense mutationCreated: 29 Jun 2018, 9:57 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Autoinflammation with arthritis and dyskeratosis
Publications
Gene: nlrp1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NLRP1 were changed from Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis, 617388 to Autoinflammation with arthritis and dyskeratosis, OMIM:617388; ?Respiratory papillomatosis, juvenile recurrent, congenital, OMIM:618803; Palmoplantar carcinoma, multiple self-healing, OMIM:615225; {Vitiligo-associated multiple autoimmune disease susceptibility 1}, OMIM:606579
Publications for gene: NLRP1 were set to 27965258; 31484767; 27662089; 29850521
Mode of pathogenicity for gene: NLRP1 was changed from None to Other
Tag Q4_23_promote_green tag was added to gene: NLRP1. Tag Q4_23_NHS_review tag was added to gene: NLRP1.
Gene: nlrp1 has been classified as Amber List (Moderate Evidence).
Source Other was added to NLRP1. Publications for gene NLRP1 were updated from 29850521; 27662089; 31484767; 27965258 to 27965258; 31484767; 27662089; 29850521 Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Phenotypes for gene: NLRP1 were changed from Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis to Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis, 617388
Publications for gene NLRP1 were updated from 27965258; 29850521 to 29850521; 27662089; 31484767; 27965258
Phenotypes for gene: NLRP1 were changed from Dyskeratosis, autoimmunity and arthritis; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis to Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis
Gene: nlrp1 has been classified as Amber List (Moderate Evidence).
Source NHS GMS was added to NLRP1.
Source North West GLH was added to NLRP1.
Source London North GLH was added to NLRP1.
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: nlrp1 has been classified as Red List (Low Evidence).
Publications for gene: NLRP1 were set to 27965258; 29850521
Mode of inheritance for gene: NLRP1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: NLRP1 were set to Dyskeratosis, autoimmunity and arthritis; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis
Publications for gene: NLRP1 were set to 27965258
Phenotypes for gene NLRP1 were set to Dyskeratosis, autoimmunity and arthritis, Autoinflammatory Disorders
NLRP1 was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018
NLRP1 was created by Louise Daugherty