Adult onset neurodegenerative disorder

Gene: PSAP

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 4:47 p.m. | Last Modified: 10 Oct 2023, 4:47 p.m.

Panel Version: 4.37

Associated with Parkinson disease 24, autosomal dominant, susceptibility to (OMIM:619491), but not associated with the same condition in Gen2Phen. PMID: 32201884 reports three PSAP variants in three unrelated families with OMIM:619491. Supportive in vitro functional studies were also presented for the reported variants. However, it would appear that there maybe variable expressivity or incomplete penetrance of the Parkinson phenotype, as two variant carrying sibs in Family 2 had extrapyramidal signs, but did not have the full Parkinsons phenotype (PMID: 32201884).

Created: 18 Apr 2023, 12:11 p.m. | Last Modified: 18 Apr 2023, 12:11 p.m.

Panel Version: 4.22

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 18 Apr 2023, 11:55 a.m. | Last Modified: 18 Apr 2023, 11:55 a.m.

Panel Version: 4.22

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Well established gene-disease association for bi-allelic variants.

Now early-onset PD reported with mono-allelic variants. 6 affecteds from 3 families. Age of onset ranges from 33-60. Functional studies: Autophagic vacuole accumulation in skin fibroblasts , a-Synuclein aggregation and PSAP retention in the ER and abnormal intracellular accumulation in iPSC-dopaminergic neurons. Mouse model for one of 1 of the variants had motor deficits and dopaminergic neurodegeneration.
Sources: Literature

Created: 5 Mar 2021, 6:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Parkinson disease, AD

Publications

• 32201884