Lipodystrophy - childhood onset
Gene: PSMA3
PMID:26524591 - Two unrelated cases with heterozygous variants in PSMA3 and PSMB8 were reported with proteasome-associated autoinflammatory syndrome (PRAAS) that includes lipodystrophy and lipid abnormalities. In addition, it was revealed from functional studies that these variants affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity.
This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
The 'digenic' tag has been added as both reported cases had variants in PSMB8 in addition to PSMA3 variants.Created: 8 Aug 2023, 12:51 p.m. | Last Modified: 8 Aug 2023, 12:53 p.m.
Panel Version: 4.40
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 in PSMB4 or PSMB8 (PMID: 26524591, 34416217) or by digenic heterozygous mutations in other proteasome encoding genes (PSMB8, PMSA3 PMID: 26524591).
PSMB9 has also been implicated in digenic cases but this is in a single familes and lipodystrophy is not reported in the autoinflammatory syndrome of carriers of biallelic loss of function mutations in PSMB9. Only DIGENIC cases of CANDLES involving PSMA3 have been reported.Created: 2 Aug 2023, 11:35 a.m. | Last Modified: 8 Aug 2023, 12:42 p.m.
Panel Version: 4.40
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
Gene: psma3 has been classified as Amber List (Moderate Evidence).
Publications for gene: PSMA3 were set to
Tag digenic tag was added to gene: PSMA3.
gene: PSMA3 was added gene: PSMA3 was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS Mode of inheritance for gene: PSMA3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PSMA3 were set to 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)