Newborns main panel

Gene: NOD2

Gene REMOVED because of specialist opinion (Andrew Gennery, Austen Worth and Kimberly Gilmour).

Created: 7 Jul 2023, 9:51 a.m. | Last Modified: 7 Jul 2023, 9:51 a.m.

Panel Version: 0.147

The mechanism of pathogenicity is loss-of-function (LOF).

Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.

Panel Version: 0.137

https://search.clinicalgenome.org/kb/genes/HGNC:5331 and patient cells which point to a disruption of NOD2 signalling pathways (Rosenbaum et al., 2011 PMID 21296813; Lee et al., 2010 PMID 20052476; Saito et al., 2017 PMID 28587749. This recent ref suggests signaling failure - https://pubmed.ncbi.nlm.nih.gov/36189261/ - loss of function.

Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.

Panel Version: 0.134

Looks like the mechanism of disease is unknown. In vitro experiments suggest variants lead to a gain of function and ligand independent activation of NOD2 (Monie et al., 2014 PMID 25093298); however, patient cell and mouse model data suggest a downregulation of NOD2 signalling pathways. So do we want LOF prioritisation? -> DB: "patient cells which point to a disruption of NOD2 signalling pathways (Rosenbaum et al., 2011 PMID 21296813; Lee et al., 2010 PMID 20052476; Saito et al., 2017 PMID 28587749." This recent ref suggests signaling failure - https://pubmed.ncbi.nlm.nih.gov/36189261/ - loss of function. There are LOF variants that seem to cause Blau.

Created: 17 May 2023, 1:42 p.m. | Last Modified: 17 May 2023, 1:42 p.m.

Panel Version: 0.83