Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: FCN3

I don't know

Eight unrelated patients from different geographic regions/ descent were identified with the same homozygous variant c.349delC. Large number of homozygotes are present in Gnomad.

Created: 1 Nov 2023, 5:42 p.m. | Last Modified: 1 Nov 2023, 5:42 p.m.

Panel Version: 4.87

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency due to ficolin 3 deficiency, OMIM:613860

Publications

• 19535802
• 20971976
• 22226667
• 25662573
• 29907670
• 31408713
• 32634042

I don't know

PMID: 32634042 appears to show a new patient with biallelic variants - can't access paper however

Created: 13 Oct 2023, 2:46 p.m. | Last Modified: 13 Oct 2023, 2:46 p.m.

Panel Version: 4.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 32634042

Red List (low evidence)

Probably not suitable for straightforward diagnostic reporting process

Created: 29 Jun 2018, 2:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Red List (low evidence)

Zornitza Stark (VCGS) , pers. comm. notes there are multiple cases reported, but single variant, and rates the gene Green. However, as highlighted by previous expert review it is not suitable for straightforward diagnostic reporting process, further evidence is needed since the consequences of FCN3 deficiency do not seem to be not clear-cut, and it has been suggested that it may act as a disease modifier.

Created: 21 Sep 2018, 12:20 p.m.

Comment on list classification: Changed from Amber to Red due to Red review from external expert, agreeing this gene for straightforward diagnostic reporting process. To be referred back to Victorian Clinical Genetics Services for evidences.

Created: 4 Jul 2018, 10:01 a.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): FCN3 .PanelApp HGNC gene symbol check: FCN3 . IUIS Disease: Ficolin 3 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Respiratory infections, abscesses. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A

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

Keep Amber until more info on gene and disease association, refer to external expert review. Only one variant reported to date, Michalski et al. (2012) PMID: 22226667 concluded that heterozygosity for the FCN3 variant does not seem to have major clinical importance PMID: 25662573, then in 2015 Michalski et al. PMID: 25662573 concluded that the consequences of FCN3 deficiency are not clear-cut, and suggested that it may act as a disease modifier.

Created: 19 Jun 2018, 10:46 a.m.

from PMID: 25662573, 19535802, Orphanet Immunodeficiency due to ficolin3 deficiency is a rare, genetic, immunodeficiency due to a complement cascade protein anomaly characterized by low or undetectable serum ficolin3 levels, susceptibility to infections, and possibly autoimmunity. The presentation is variable, from perinatal necrotizing enterocolitis and recurrent skin infections with Staphylococcus aureus to childhood-onset recurrent pulmonary infections leading to brain abscesses and pulmonary fibrosis, to membranous nephropathy. In some patients, clinical consequences of ficolin3 deficiency were not clear.

Created: 19 Jun 2018, 10:39 a.m.

Comment on publications: added publications to support the phenotype

Created: 19 Jun 2018, 10:39 a.m.

Comment on mode of inheritance: added MOI from PMID: 20971976

Created: 19 Jun 2018, 10:36 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: FCN3, PanelApp HGNC gene symbol check: FCN3, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Ficolin3 deficiency

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: FCN3, GRID_Gene_Symbol: FCN3, GRID_Transcript_ENS_Community submitted: ENST00000270879, GRID_Transcript_RefSeq: NM_003665.2, GRID_Transcript_ENS_used_on_Production: ENST00000270879

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