Autoinflammatory disorders

Gene: PSMB4

Green List (high evidence)

This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.

Created: 16 Feb 2022, 11:44 a.m. | Last Modified: 16 Feb 2022, 11:44 a.m.

Panel Version: 0.36

PSMB4 is rated Amber on the PID panel (R15, version 2.524) and the OMIM entry for this phenotype (MIM# 617591) is currently set to provisional.

Brehm et al., 2015 (PMID: 26524591) describes a patient with compound heterozygous variants in this gene including a 9 bp inframe deletion and a point variant in the 5′ UTR. A further two unrelated families with two affected sibs each were also identified by targeted screening of proteasome candidate genes with different monoallelic PSMB4 variants in conjunction with a monoallelic variant in PSMB9 or PSMB8, respectively (i.e. digenic inheritance). All individuals had a clinical phenotype of CANDLE syndrome.

Verhoeven et al., 2021 (PMID: 34416217) reports a second individual with novel compound heterozygous variants in this gene who presented at 2 months of age with an autoinflammatory disorder which was alleviated following treatment by hematopoietic stem cell transplantation.

Created: 11 Jan 2022, 12:08 p.m. | Last Modified: 11 Jan 2022, 12:08 p.m.

Panel Version: 0.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteasome-associated autoinflammatory syndrome 3 and digenic forms, OMIM:617591

Publications

• 34416217
• 26524591