Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PRF1

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green 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, 1:41 p.m. | Last Modified: 14 Oct 2020, 1:41 p.m.

Panel Version: 2.295

The following PubMed IDs were added to entity PRF1: 10583959;22248322;28468610;28806468. These publications have been associated with OMIM phenotype MIM#603553, which is listed for this entity, by the immunedysregulation 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

• 10583959
• 22248322
• 28468610
• 28806468

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

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

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): PRF1 .PanelApp HGNC gene symbol check: PRF1 . IUIS Disease: Perforin deficiency (FHL2) . IUIS Inheritance: AR .T cells: Nl number, low nave T cells, restricted repertoire, poor proliferation to CD3, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Fever, HSM, Hemophagocytic lymphohistiocytosis (HLH), cytopenias. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes)

Created: 2 Jul 2018, 10:35 a.m.

from GeneReview PMID:20301617 20%-30% of Worldwide cases of FHL are FHL2 (PMID:15365097, PMID:15632205) and 50% in African American families 4 are FHL2 (PMID:14757862, PMID:16860143)

Created: 30 Apr 2018, 10:24 a.m.

Comment on publications: added genereview

Created: 30 Apr 2018, 10:17 a.m.

added early-onset tag

Created: 30 Apr 2018, 10:04 a.m.

Comment on list classification: Changed status from Amber to Green, there are more than 3 unrelated cases to support the phenotype Familial hemophagocytic lymphohistiocytosis-2 (FHL2) caused by homozygous or compound heterozygous mutation in the gene encoding perforin PRF1. Publications include: Goransdotter Ericson et al. (2001) PMID:11179007, where FHL2 was confirmed by genetic analysis reported 7 unrelated families. In PMID:10583959 Stepp et al. (1999) reported 8 unrelated patients with familial hemophagocytic lymphohistiocytosis linked to 10q21-q22, they sequenced the coding region of the PRF1 gene and identified homozygous nonsense mutations in 4 patients and missense mutations in the other 4 patients.

Created: 30 Apr 2018, 9:51 a.m.

Comment on publications: Added publications to support role of PRF1 variants in Hemophagocytic lymphohistiocytosis, familial, 2

Created: 30 Apr 2018, 9:43 a.m.

From OMIM: Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia.

Created: 30 Apr 2018, 9:41 a.m.

Comment on phenotypes: added synonyms

Created: 30 Apr 2018, 9:37 a.m.

Comment on phenotypes: added OMIM MIMid

Created: 30 Apr 2018, 9:35 a.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: PRF1, PanelApp HGNC gene symbol check: PRF1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Hemophagocytic Lymphohistiocytosis (HLH) / Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: PRF1, GRID_Gene_Symbol: PRF1, GRID_Transcript_ENS_Community submitted: ENST00000441259, GRID_Transcript_RefSeq: NM_001083116.1, GRID_Transcript_ENS_used_on_Production: ENST00000441259

Created: 17 Apr 2018, 12:12 p.m.

Publications

• 11179007
• 10583959
• 12229880
• 14757862
• 14757862