Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CSF2RA

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)

3 patients in 2 kindreds, plus evidence that the ligand for this receptor prevents pulmonary alveolar proteinosis (anti-GM-CSF antibodies also cause PAP). This is fundamentally a disorder of alveolar macrophage function and listed as such in the IUIS classification.

Created: 11 Jun 2018, 2:58 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
pulmonary alveolar proteinosis

Publications

• 18955567
• 18955570

Green List (high evidence)

Comment on mode of inheritance: Changed MOI due to MOI checks carried out by PanelApp team. This gene is on the pseudoautosomal region of chromosome X which is shared with chromoseome Y, so MOI affected cases are biallelic.

Created: 12 Nov 2019, 1:49 p.m. | Last Modified: 12 Nov 2019, 1:49 p.m.

Panel Version: 1.137

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): CSF2RA .PanelApp HGNC gene symbol check: CSF2RA . IUIS Disease: Congenital pulmonary alveolar proteinosis due to CSF2RA mutations . IUIS Inheritance: XL (Pseudoautosomal) .T cells: Low, poor proliferation, few, poorly functioning Treg , .B cells: N/A, .IUIS Other affected cells: Alveolar macrophages. IUIS Associated features: Alveolar proteinosis. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Other Non-Lymphoid Defects

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

Comment on list classification: Upon further review and understanding of the disorder of alveolar macrophage function and the affect on immunity, I agree that the status for this gene should be upgraded from Red to Green due to external review comment and further publications to support although only 2 unrelated families reported in the literature (3 affected) there is evidence that the ligand for this receptor prevents pulmonary alveolar proteinosis (anti-GM-CSF antibodies also cause PAP)

Created: 12 Jun 2018, 12:37 p.m.

Comment on mode of inheritance: Added MOI from external expert review

Created: 12 Jun 2018, 12:33 p.m.

Comment on list classification: changed from Amber to Red- not enough evidence to support immune dysfunction

Created: 4 Jun 2018, 11:18 a.m.

Comment on publications: added publications that associate gene to Allergic hypersensitivity disease

Created: 4 Jun 2018, 11:04 a.m.

Not strong PID. From OMIM Gough et al. (1990) PMID: 1972780 showed showed that the gene for the alpha subunit of the granulocyte-macrophage colony-stimulating factor (CSF2R) maps to the tip of the short arm of the X chromosome and to the short arm of the Y chromosome. Loss of either the X or the Y chromosome is apparent in 25% of acute myeloid leukemias of the M2 subtype (AML-M2), compared with only 1 to 6% of other AML subtypes, suggesting the involvement of a 'recessive oncogene' in the genesis of M2 AMLs. The presumed gene is likely to be in the PAR, because if it were located in the portion of the X chromosome not shared with the Y, then similar loss of the Y chromosome would not be predicted and vice versa. Gough et al. (1990) suggested that CSF2R may be the gene in question. Loss or inactivation of both copies of the gene in a myeloid progenitor cell would be expected to result in a clone of cells unable to respond to GM-CSF, and hence in the relatively undifferentiated phenotype of the M2 form of leukemia.

Created: 4 Jun 2018, 11 a.m.

Comment on publications: added publications to support Pulmonary alveolar proteinosis. PMID: 18955567 the first report of PAP resulting from a genetic deficiency of GM-CSFRalpha. PMID: 18955570 the second (two affected sisters). There is no third case in the literature.

Created: 4 Jun 2018, 10:39 a.m.

Comment on mode of inheritance: CSF2RA located on Xp22.32 and Yp11.3. IUIS mode of inheritance Biallelic mutations in pseudo-autosomal gene

Created: 4 Jun 2018, 10:30 a.m.

Comment on phenotypes: added MIMid from OMIM, and phenotype from Orphanet.

Created: 4 Jun 2018, 10:15 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: CSF2RA, PanelApp HGNC gene symbol check: CSF2RA, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / Pulmonary alveolar proteinosis / Pulmonary alveolar proteinosis

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CSF2RA, GRID_Gene_Symbol: CSF2RA, GRID_Transcript_ENS_Community submitted: ENST00000432318, GRID_Transcript_RefSeq: NM_001161529.1, GRID_Transcript_ENS_used_on_Production: ENST00000432318

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