Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from biallelic to monoallelic as all cases reported to date have harboured heterozygous variants in this gene (PMID: 26524591; 33727065; 34819510)
Arina Puzriakova Mode of inheritance for gene: PSMB9 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Arina Puzriakova edited their review of gene: PSMB9: Added comment: Kanazawa et al., 2021 (PMID: 34819510) identified a further two unrelated Japanese patients with the same de novo PSMB9 heterozygous missense variant as that identified in the previous study (c.467G>A/p.G156D). Both individuals displayed severe autoinflammatory phenotypes and pulmonary hypertension and later also manifested combined immunodeficiency with periodic inflammatory exacerbation. The variant lead to impaired immunoproteasome maturation and activity, and the proteasome defect and immunodeficient phenotypes were recapitulated in Psmb9(G156D/+) mice.; Changed publications to: 33727065, 34819510; Changed phenotypes to: Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591
Arina Puzriakova Phenotypes for gene: PSMB9 were changed from Autoinflammation, lipodystrophy, and dermatosis syndrome; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) to Proteasome-associated autoinflammatory syndrome 3, digenic, OMIM:617591; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
Louise Daugherty commented on gene: PSMB9: 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.
Louise Daugherty commented on gene: PSMB9: ?Proteasome-associated autoinflammatory syndrome 3, digenic. One patient, one similar patient het for this and another gene (PSMB4) hence ?digenic - amber on association
Louise Daugherty commented on gene: PSMB4: ?Proteasome-associated autoinflammatory syndrome 3, digenic. One patient het for this and another gene (PSMB9) hence ?digenic - amber on association
Louise Daugherty changed review comment from: Comment on list classification: Changed rating from Red to Amber to reflect the agreed rating agreed by the GMS Immunology Specialist Test Group; to: Comment on list classification: Changed rating from Red to Amber to reflect the agreed rating agreed by the GMS Immunology Specialist Test Group, but flagged for further follow up with the Immunology Test Group due to the subsequent conflicting review. Evidence /opinion needs consensus before upgrading to Green
Louise Daugherty changed review comment from: Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. Although discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 to rate Amber in the confirmed follow up email on 20th June North West GLH reasserted that PSMA3 should be Green; to: Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. Although discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 to rate Amber in the confirmed follow up email on 20th June North West GLH reasserted that PSMB9 should be Green
Louise Daugherty changed review comment from: 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 only enough evidence to rate this gene Amber.; to: Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. Although discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 to rate Amber in the confirmed follow up email on 20th June North West GLH reasserted that PSMA3 should be Green
Louise Daugherty Added comment: Comment on list classification: Changed rating from Red to Amber to reflect the agreed rating agreed by the GMS Immunology Specialist Test Group
Louise Daugherty commented on gene: PSMB9: 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 only enough evidence to rate this gene Amber.
Louise Daugherty edited their review of gene: PSMB9: Added comment: 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 only enough evidence to rate this gene Amber; Changed rating: AMBER
Louise Daugherty changed review comment from: Comment on publications: PMID:26524591 suggested by Tracy Briggs (NWGLH) on behalf of The Specialist Test Group to support inclusion of this gene on the panel.; to: Comment on publications: PMID:26524591 suggested by Tracy Briggs (NWGLH) on behalf of the Specialist Test Group to support inclusion of this gene on the panel and a Green rating. Flagged for further discussion with the Specialist Test Group as conflicts with the Amber rating agreed in the webex 28th March 2019. Added digenic tag - from review comment 'Digenic also reported'.
Louise Daugherty Phenotypes for gene: PSMB9 were changed from CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome) to Autoinflammation, lipodystrophy, and dermatosis syndrome; CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome)
Louise Daugherty Added comment: Comment on publications: PMID:26524591 suggested by Tracy Briggs (NWGLH) on behalf of The Specialist Test Group to support inclusion of this gene on the panel.