Lipodystrophy - childhood onset

Gene: PSMB8

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 31 Dec 2025, 7:17 p.m. | Last Modified: 31 Dec 2025, 7:17 p.m.

Panel Version: 4.66

This gene is approved to upgrade to Green when TD eligibility and Clinical Indication name is expanded to Severe insulin resistance and lipodystrophy syndromes.

Created: 17 Jun 2024, 8:59 a.m. | Last Modified: 17 Jun 2024, 8:59 a.m.

Panel Version: 4.54

Comment on list classification: There is sufficient evidence available for this gene to be promoted to green rating at the next GMS review.

Created: 8 Aug 2023, 10:50 a.m. | Last Modified: 8 Aug 2023, 10:50 a.m.

Panel Version: 4.37

The 'digenic' tag has been added as there are four digenic cases reported (two cases each with heterozygous variants in PSMA3/ PSMB8 and PSMB4/ PSMB8) in addition to patients with homozygous PSMB8 variants.

Created: 8 Aug 2023, 10:49 a.m. | Last Modified: 8 Aug 2023, 11:39 a.m.

Panel Version: 4.40

PMID:21129723 - A homozygous missense variant (c.224C>T/ p.Thr75Met) in PSMB8 gene was identified in affected patients from two different families with an autosomal-recessive autoinflammatory syndrome characterised by joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced lipodystrophy (JMP).

PMID:21953331 - Of nine patients from eight families reported in this publication with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome), four patients were homozygous and two were heterozygous for the previously reported missense variant (c.224C>T), one had no PSMB8 variant and one patient was homozygous for a novel nonsense variant (c.405C>A).

This gene has been associated with relevant phenotypes in OMIM (MIM #256040) and Gene2Phenotype ('definitive' rating in the DD panel for Nakajo syndrome) and lipodystrophy has been included as a part of this phenotype in these resources.

Created: 8 Aug 2023, 10:42 a.m. | Last Modified: 8 Aug 2023, 10:42 a.m.

Panel Version: 4.34

This gene was added on recommendation of NHSE Genomic Medicine Service:
These autoinflammatory syndromes include a lipodystrophy (partial and generalised have both been reported) and are caused either by biallelic loss of function mutations (PMID: 20534754, 21129723, 21953331) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB4, PSMA3)(PMID: 26524591).

PSMB9 has also been implicated in digenic causes but these are in single kindreds and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9.

Created: 2 Aug 2023, 11:35 a.m. | Last Modified: 8 Aug 2023, 8:52 a.m.

Panel Version: 4.34

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteasome associated autoinflammatory syndrome-1, CANDLES (Chronic, atypical, neutrophillic dermatosis with lipodystrophy and elevated temperature syndrome), Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome)

Publications

• 20534754
• 21129723
• 21953331
• 26524591