Adult onset hereditary spastic paraplegia
Gene: PRNP
Amongst the variable phenotypes seen in carriers of PRNP variants, features of Gerstmann-Straussler disease (OMIM: 137440) have been associated with eight PRNP variants in unrelated cases (p.P105L, p.D178N, p.P102L, p.A117V, p.F198S, p.Q217R, p.G131V, p.H187R (PMIDs: 7902971, 1699173, 1363810, 11709001, 7902972, 19228673).Created: 8 Jun 2023, 11:22 a.m. | Last Modified: 8 Jun 2023, 11:22 a.m.
Panel Version: 3.10
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 8 Jun 2023, 11:02 a.m. | Last Modified: 8 Jun 2023, 11:02 a.m.
Panel Version: 3.7
Phenotypes
Gerstmann-Straussler disease, OMIM: 137440
HSP can be a rare presenting phenotype for some individuals with inherited prion disease.
Sources: NHS GMSCreated: 31 May 2023, 12:54 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
HSP; Gerstmann–Sträussler–Scheinker disease
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183; 1363810
Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183
Phenotypes for gene: PRNP were changed from Gerstmann-Straussler disease, OMIM: 137440 to Gerstmann-Straussler disease, OMIM: 137440; Gerstmann-Straussler-Scheinker syndrome, MONDO:0007656
Gene: prnp has been classified as Amber List (Moderate Evidence).
Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673
Tag Q3_23_promote_green tag was added to gene: PRNP.
Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350
Phenotypes for gene: PRNP were changed from HSP; Gerstmann–Sträussler–Scheinker disease to Gerstmann-Straussler disease, OMIM: 137440
gene: PRNP was added gene: PRNP was added to Adult onset hereditary spastic paraplegia. Sources: NHS GMS Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350 Phenotypes for gene: PRNP were set to HSP; Gerstmann–Sträussler–Scheinker disease Penetrance for gene: PRNP were set to Complete Mode of pathogenicity for gene: PRNP was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PRNP was set to GREEN gene: PRNP was marked as current diagnostic